text:
Altered brain activity for phonological manipulation in dyslexic Japanese children
Yamamoto, Hisako; Oba, Kentaro; Terasawa, Yuri; Moriguchi, Yoshiya; Uchiyama, Hitoshi; Seki, Ayumi; Koeda, Tatsuya; Inagaki, Masumi
Because of unique linguistic characteristics, the prevalence rate of developmental dyslexia is relatively low in the Japanese language. Paradoxically, Japanese children have serious difficulty analysing phonological processes when they have dyslexia. Neurobiological deficits in Japanese dyslexia remain unclear and need to be identified, and may lead to better understanding of the commonality and diversity in the disorder among different linguistic systems. The present study investigated brain activity that underlies deficits in phonological awareness in Japanese dyslexic children using functional magnetic resonance imaging. We developed and conducted a phonological manipulation task to extract phonological processing skills and to minimize the influence of auditory working memory on healthy adults, typically developing children, and dyslexic children. Current experiments revealed that several brain regions participated in manipulating the phonological information including left inferior and middle frontal gyrus, left superior temporal gyrus, and bilateral basal ganglia. Moreover, dyslexic children showed altered activity in two brain regions. They showed hyperactivity in the basal ganglia compared with the two other groups, which reflects inefficient phonological processing. Hypoactivity in the left superior temporal gyrus was also found, suggesting difficulty in composing and processing phonological information. The altered brain activity shares similarity with those of dyslexic children in countries speaking alphabetical languages, but disparity also occurs between these two populations. These are initial findings concerning the neurobiological impairments in dyslexic Japanese children. PMID:24052613
On Altered Patterns of Brain Activation in At-Risk Adolescents and Young Adults
Editorial On Altered Patterns of Brain Activation in At-Risk Adolescents and Young Adults activity in 60 adolescents and young adults at risk for psychosis and 38 healthy comparison subjects, using in individuals diagnosed with or at risk for schizophrenia. Thus, we focus our comments on the findings
Altered host behaviour and brain serotonergic activity caused by acanthocephalans: evidence for specificity
Tain, Luke; Perrot-Minnot, Marie-Jeanne; Cézilly, Frank
Manipulative parasites can alter the phenotype of intermediate hosts in various ways. However, it is unclear whether such changes are just by-products of infection or adaptive and enhance transmission to the final host. Here, we show that the alteration of serotonergic activity is functionally linked to the alteration of specific behaviour in the amphipod Gammarus pulex infected with acanthocephalan parasites. Pomphorhynchus laevis and, to a lesser extent, Pomphorhynchus tereticollis altered phototactism, but not geotactism, in G. pulex, whereas the reverse was true for Polymorphus minutus. Serotonin (5-hydroxytryptamine, 5-HT) injected to uninfected G. pulex mimicked the altered phototactism, but had no effect on geotactism. Photophilic G. pulex infected with P. laevis or P. tereticollis showed a 40% increase in brain 5-HT immunoreactivity compared to photophobic, uninfected individuals. In contrast, brain 5-HT immunoreactivity did not differ between P. minutus-infected and uninfected G. pulex. Finally, brain 5-HT immunoreactivity differed significantly among P. tereticollis-infected individuals in accordance with their degree of manipulation. Our results demonstrate that altered 5-HT activity is not the mere consequence of infection by acanthocephalans but is specifically linked to the disruption of host photophobic behaviour, whereas the alteration of other behaviours such as geotactism may rely on distinct physiological routes. PMID:17015346
First demonstration that brain CYP2D-mediated opiate metabolic activation alters analgesia in vivo
Zhou, Kaidi; Khokhar, Jibran Y.; Zhao, Bin; Tyndale, Rachel F.
The response to centrally-acting drugs is highly variable between individuals and does not always correlate with plasma drug levels. Drug-metabolizing CYP enzymes in the brain may contribute to this variability by affecting local drug and metabolite concentrations. CYP2D metabolizes codeine to the active morphine metabolite. We investigate the effect of inhibiting brain, and not liver, CYP2D activity on codeine-induced analgesia. Rats received intracerebroventricular injections of CYP2D inhibitors (20 ?g propranolol or 40 ?g propafenone) or vehicle controls. Compared to vehicle-pretreated rats, inhibitor-pretreated rats had: a) lower analgesia in the tail-flick test (p<0.05) and lower areas under the analgesia-time curve (p<0.02) within the first hour after 30 mg/kg subcutaneous codeine, b) lower morphine concentrations and morphine to codeine ratios in the brain (p<0.02 and p<0.05, respectively), but not in plasma (p>0.6 and p>0.7, respectively), tested at 30 min after 30 mg/kg subcutaneous codeine, and c) lower morphine formation from codeine ex vivo by brain membranes (p<0.04), but not by liver microsomes (p>0.9). Analgesia trended toward a correlation with brain morphine concentrations (p=0.07) and correlated with brain morphine to codeine ratios (p<0.005), but not with plasma morphine concentrations (p>0.8) or plasma morphine to codeine ratios (p>0.8). Our findings suggest that brain CYP2D affects brain morphine levels after peripheral codeine administration, and may thereby alter codeine's therapeutic efficacy, side-effect profile and abuse liability. Brain CYPs are highly variable due to genetics, environmental factors and age, and may therefore contribute to interindividual variation in the response to centrally-acting drugs. PMID:23623752
Altered spontaneous brain activity in patients with hemifacial spasm: a resting-state functional MRI study.
Tu, Ye; Wei, Yongxu; Sun, Kun; Zhao, Weiguo; Yu, Buwei
Resting-state functional magnetic resonance imaging (fMRI) has been used to detect the alterations of spontaneous neuronal activity in various neurological and neuropsychiatric diseases, but rarely in hemifacial spasm (HFS), a nervous system disorder. We used resting-state fMRI with regional homogeneity (ReHo) analysis to investigate changes in spontaneous brain activity of patients with HFS and to determine the relationship of these functional changes with clinical features. Thirty patients with HFS and 33 age-, sex-, and education-matched healthy controls were included in this study. Compared with controls, HFS patients had significantly decreased ReHo values in left middle frontal gyrus (MFG), left medial cingulate cortex (MCC), left lingual gyrus, right superior temporal gyrus (STG) and right precuneus; and increased ReHo values in left precentral gyrus, anterior cingulate cortex (ACC), right brainstem, and right cerebellum. Furthermore, the mean ReHo value in brainstem showed a positive correlation with the spasm severity (r = 0.404, p = 0.027), and the mean ReHo value in MFG was inversely related with spasm severity in HFS group (r = -0.398, p = 0.028). This study reveals that HFS is associated with abnormal spontaneous brain activity in brain regions most involved in motor control and blinking movement. The disturbances of spontaneous brain activity reflected by ReHo measurements may provide insights into the neurological pathophysiology of HFS. PMID:25603126
Altered Error-Related Brain Activity in Youth with Major Depression
Ladouceur, Cecile D.; Slifka, John S.; Dahl, Ronald E.; Birmaher, Boris; Axelson, David A.; Ryan, Neal D.
Depression is associated with impairments in cognitive control including action monitoring processes, which involve the detection and processing of erroneous responses in order to adjust behavior. Although numerous studies have reported altered error-related brain activity in depressed adults, relatively little is known about age-related changes in error-related brain activity in depressed youth. This study focuses on the error-related negativity (ERN), a negative deflection in the event-related potential (ERP) that is maximal approximately 50 ms following errors. High-density ERPs were examined following responses on a flanker task in 24 youth diagnosed with MDD and 14 low-risk healthy controls (HC). Results indicate that compared to HC, MDD youth had significantly smaller ERN amplitudes and did not exhibit the normative increases in ERN amplitudes as a function of age. Also, ERN amplitudes were similar in depressed youth with and without comorbid anxiety. These results suggest that depressed youth exhibit different age-related changes in brain activity associated with action monitoring processes. Findings are discussed in terms of existing work on the neural correlates of action monitoring and depression and the need for longitudinal research studies investigating the development of neural systems underlying action monitoring in youth diagnosed with and at risk for depression. PMID:22669036
Altered baseline brain activity differentiates regional mechanisms subserving biological and psychological alterations in obese men
Zhang, Bin; Tian, Derun; Yu, Chunshui; Li, Meng; Zang, Yufeng; Liu, Yijun; Walter, Martin
Obesity as a chronic disease is a major factor for insulin resistance and Type 2 diabetes, which has become a global health problem. In the present study, we used resting state functional MRI to investigate the amplitude of low frequency fluctuations of spontaneous signal during both hunger and satiety states in 20 lean and 20 obese males. We found that, before food intake, obese men had significantly greater baseline activity in the precuneus and lesser activity in dorsal anterior cingulate cortex (dACC) relative to lean subjects. Furthermore, after food intake, obese males had significantly lesser activity in dACC than lean males. We further found a significant positive correlation between precuneus activation and hunger ratings before food intake, while dACC activity was negatively correlated with plasma insulin levels before and after food intake. These results indicated that both precuneus and dACC may play an important role in eating behavior. While precuneus rather seemed to mediate subjective satiety, dACC levels rather reflected indirect measures of glucose utilization. PMID:26099208
Distinct mechanisms of altered brain activation in patients with multiple sclerosis.
Morgen, Katrin; Sammer, Gebhard; Courtney, Susan M; Wolters, Tobias; Melchior, Hanne; Blecker, Carlo R; Oschmann, Patrick; Kaps, Manfred; Vaitl, Dieter
Cerebral reorganization may limit the effects of central nervous system tissue damage on cognition in patients with multiple sclerosis (MS). This study investigated fMRI activation patterns in patients with relapsing-remitting MS and healthy control subjects during performance of a delayed recognition task. As intended, fMRI task performance was similar in the MS and the control group, whereas neuropsychological testing revealed reduced performance in the patient group on the Paced Serial Addition Test, a reference task for the assessment of cognitive function in MS. Patients overall showed more activation in left posterior parietal cortex than healthy control subjects. Global gray matter atrophy in the patient group was associated with low PASAT scores. In a multiple regression analysis including white matter lesion load and gray matter atrophy as covariates, PASAT performance correlated with activation in left posterior parietal cortex and right anterior midfrontal gyrus, indicating a reallocation of neuronal resources to help preserve function. Global gray matter atrophy correlated with activation in bilateral prefrontal cortex, dorsal ACC and left posterior parietal cortex and, furthermore, was associated with a low degree of deactivation in rostral ACC, suggesting neural inefficiency and consistent with a reduced capacity to modulate between frontoparietal task-associated activation and 'default network' activity. The current study provides evidence that altered brain activation in MS patients has two distinct components, one related to compensatory processes and one to neural inefficiency associated with tissue damage. PMID:17627848
Altered Spontaneous Brain Activity in Schizophrenia: A Meta-Analysis and a Large-Sample Study
Xu, Yongjie; Zhuo, Chuanjun; Qin, Wen; Zhu, Jiajia; Yu, Chunshui
Altered spontaneous brain activity as measured by ALFF, fALFF, and ReHo has been reported in schizophrenia, but no consensus has been reached on alternations of these indexes in the disorder. We aimed to clarify the regional alterations in ALFF, fALFF, and ReHo in schizophrenia using a meta-analysis and a large-sample validation. A meta-analysis of activation likelihood estimation was conducted based on the abnormal foci of ten studies. A large sample of 86 schizophrenia patients and 89 healthy controls was compared to verify the results of the meta-analysis. Meta-analysis demonstrated that the alternations in ALFF and ReHo had similar distribution in schizophrenia patients. The foci with decreased ALFF/fALFF and ReHo in schizophrenia were mainly located in the somatosensory cortex, posterior parietal cortex, and occipital cortex; however, foci with increased ALFF/fALFF and ReHo were mainly located in the bilateral striatum, medial temporal cortex, and medial prefrontal cortex. The large-sample study showed consistent findings with the meta-analysis. These findings may expound the pathophysiological hypothesis and guide future research. PMID:26180786
Choline-deprivation alters crucial brain enzyme activities in a rat model of diabetic encephalopathy.
Liapi, Charis; Kyriakaki, Argyro; Zarros, Apostolos; Galanopoulou, Panagiota; Al-Humadi, Hussam; Dontas, Ismene; Voumvourakis, Konstantinos; Tsakiris, Stylianos
Diabetic encephalopathy describes the moderate cognitive deficits, neurophysiological and structural central nervous system changes associated with untreated diabetes. It involves neurotoxic effects such as the generation of oxidative stress, the enhanced formation of advanced glycation end-products, as well as the disturbance of calcium homeostasis. Due to the direct connection of choline (Ch) with acetylcholine availability and signal transduction, a background of Ch-deficiency might be unfavorable for the pathology and subsequently for the treatment of several metabolic brain diseases, including that of diabetic encephalopathy. The aim of this study was to shed more light on the effects of adult-onset streptozotocin (STZ)-induced diabetes and/or Ch-deprivation on the activities of acetylcholinesterase (AChE) and two important adenosine triphosphatases, namely Na(+),K(+)-ATPase and Mg(2+)-ATPase. Male adult Wistar rats were divided into four main groups, as follows: control (C), diabetic (D), Ch-deprived (CD), and Ch-deprived diabetic (D+CD). Deprivation of Ch was provoked through the administration of Ch-deficient diet. Both the induction of diabetes and the beginning of dietary-mediated provoking of Ch-deprivation occurred at the same day, and rats were killed by decapitation after 30 days (1 month; groups C1, D1, CD1 and D1+CD1) and 60 days (2 months; groups C2, D2, CD2 and D2+CD2, respectively). The adult rat brain AChE activity was found to be significantly increased by both diabetes (+10%, p < 0.001 and +11%, p < 0.01) and Ch-deprivation (+19%, p < 0.001 and +14%, p < 0.001) when compared to the control group by the end of the first (C1) and the second month (C2), respectively. However, the Ch-deprived diabetic rats' brain AChE activity was significantly altered only after a 60-day period of exposure, resulting in a +27% increase (D2+CD2 vs. C2, p < 0.001). Although the only significant change recorded in the brain Na(+),K(+)-ATPase activity after the end of the first month is attributed to Ch-deprivation (+21%, p < 0.05, CD1 vs. C1), all groups of the second month exhibited a statistically significant decrease in brain Na(+),K(+)-ATPase activity (-24%, p < 0.01, D2 vs. C2; -21%, p < 0.01, CD2 vs. C2; -22%, p < 0.01, D2+CD2 vs. C2). As concerns Mg(2+)-ATPase, the enzyme's activity demonstrates no significant changes, with the sole exception of the D2+CD2 group (+21%, p < 0.05, D2+CD2 vs. C2). In addition, statistically significant time-dependent changes concerning the brain Mg(2+)-ATPase activity were recorded within the diabetic (p < 0.05, D2 vs. D1) and the Ch-deprived (p < 0.05, CD2 vs. CD1) rat groups. Our data indicate that Ch-deprivation seems to be an undesirable background for the above-mentioned enzymatic activities under untreated diabetes, in a time-evolving way. Further studies on the issue should focus on a region-specific reevaluation of these crucial enzymes' activities as well as on the possible oxidative mechanisms involved. PMID:20838865
Roux-en-Y Gastric Bypass Alters Brain Activity in Regions that Underlie Reward and Taste Perception
Thanos, Panayotis K.; Michaelides, Mike; Subrize, Mike; Miller, Mike L.; Bellezza, Robert; Cooney, Robert N.; Leggio, Lorenzo; Wang, Gene-Jack; Rogers, Ann M.; Volkow, Nora D.; Hajnal, Andras
Background Roux-en-Y gastric bypass (RYGB) surgery is a very effective bariatric procedure to achieve significant and sustained weight loss, yet little is known about the procedure's impact on the brain. This study examined the effects of RYGB on the brain's response to the anticipation of highly palatable versus regular food. Methods High fat diet-induced obese rats underwent RYGB or sham operation and were then tested for conditioned place preference (CPP) for the bacon-paired chamber, relative to the chow-paired chamber. After CPP, animals were placed in either chamber without the food stimulus, and brain-glucose metabolism (BGluM) was measured using positron emission tomography (?PET). Results Bacon CPP was only observed in RYGB rats that had stable weight loss following surgery. BGluM assessment revealed that RYGB selectively activated regions of the right and midline cerebellum (Lob 8) involved in subjective processes related to reward or expectation. Also, bacon anticipation led to significant activation in the medial parabrachial nuclei (important in gustatory processing) and dorsomedial tegmental area (key to reward, motivation, cognition and addiction) in RYGB rats; and activation in the retrosplenial cortex (default mode network), and the primary visual cortex in control rats. Conclusions RYGB alters brain activity in areas involved in reward expectation and sensory (taste) processing when anticipating a palatable fatty food. Thus, RYGB may lead to changes in brain activity in regions that process reward and taste-related behaviors. Specific cerebellar regions with altered metabolism following RYGB may help identify novel therapeutic targets for treatment of obesity. PMID:26039080
The hyperactive syndrome: Metanalysis of genetic alterations, pharmacological treatments and brain lesions which increase locomotor activity
Davide Viggiano
The large number of transgenic mice realized thus far with different purposes allows addressing new questions, such as which animals, over the entire set of transgenic animals, show a specific behavioural abnormality. In the present study, we have used a metanalytical approach to organize a database of genetic modifications, brain lesions and pharmacological interventions that increase locomotor activity in animal
Estradiol treatment altered anticholinergic-related brain activation during working memory in postmenopausal women
Dumas, Julie A.; Kutz, Amanda M.; Naylor, Magdalena R.; Johnson, Julia V.; Newhouse, Paul A.
Estradiol has been shown to affect cholinergic modulation of cognition in human and nonhuman animal models. This study examined the brain-based interaction of estradiol treatment and anticholinergic challenge in postmenopausal women during the performance of a working memory task and functional MRI. Twenty-four postmenopausal women were randomly and blindly placed on 1 mg oral 17-? estradiol or matching placebo pills for three months after which they participated in three anticholinergic challenge sessions. During the challenge sessions, subjects were administered the antimuscarinic drug scopolamine, the antinicotinic drug mecamylamine, or placebo. After drug administration, subjects completed a fMRI session during which time they performed a visual verbal N-back test of working memory. Results showed that scopolamine increased activation in the left medial frontal gyrus (BA 10) and mecamylamine increased activation in the left inferior frontal gyrus (BA 46). Estradiol treatment compared to placebo treatment significantly reduced the activation in this left medial frontal region during scopolamine challenge. Estradiol treatment also increased activation in the precuneus (BA 31) during mecamylamine challenge. These data are the first to show that estradiol modulated antimuscarinic- and anitnicotinic-induced brain activity and suggest that estradiol affected cholinergic system regulation of cognition-related brain activation in humans. PMID:22266175
Brain Activation During Working Memory Is Altered in Patients With Type 1 Diabetes During Hypoglycemia
Bolo, Nicolas R.; Musen, Gail; Jacobson, Alan M.; Weinger, Katie; McCartney, Richard L.; Flores, Veronica; Renshaw, Perry F.; Simonson, Donald C.
OBJECTIVE To investigate the effects of acute hypoglycemia on working memory and brain function in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Using blood oxygen level–dependent (BOLD) functional magnetic resonance imaging during euglycemic (5.0 mmol/L) and hypoglycemic (2.8 mmol/L) hyperinsulinemic clamps, we compared brain activation response to a working-memory task (WMT) in type 1 diabetic subjects (n = 16) with that in age-matched nondiabetic control subjects (n = 16). Behavioral performance was assessed by percent correct responses. RESULTS During euglycemia, the WMT activated the bilateral frontal and parietal cortices, insula, thalamus, and cerebellum in both groups. During hypoglycemia, activation decreased in both groups but remained 80% larger in type 1 diabetic versus control subjects (P < 0.05). In type 1 diabetic subjects, higher HbA1c was associated with lower activation in the right parahippocampal gyrus and amygdala (R2 = 0.45, P < 0.002). Deactivation of the default-mode network (DMN) also was seen in both groups during euglycemia. However, during hypoglycemia, type 1 diabetic patients deactivated the DMN 70% less than control subjects (P < 0.05). Behavioral performance did not differ between glycemic conditions or groups. CONCLUSIONS BOLD activation was increased and deactivation was decreased in type 1 diabetic versus control subjects during hypoglycemia. This higher level of brain activation required by type 1 diabetic subjects to attain the same level of cognitive performance as control subjects suggests reduced cerebral efficiency in type 1 diabetes. PMID:21984582
Traumatic alterations in GABA signaling disrupt hippocampal network activity in the developing brain
Dzhala, Volodymyr; Valeeva, Guzel; Glykys, Joseph; Khazipov, Rustem; Staley, Kevin
Severe head trauma causes widespread neuronal shear injuries and acute seizures. Shearing of neural processes might contribute to seizures by disrupting the transmembrane ion gradients that subserve normal synaptic signaling. To test this possibility, we investigated changes in intracellular chloride concentration ([Cl?]i) associated with the widespread neural shear injury induced during preparation of acute brain slices. In hippocampal slices and intact hippocampal preparations from immature CLM-1 mice, increases in [Cl?]i correlated with disruption of neural processes and biomarkers of cell injury. Traumatized neurons with higher [Cl?]i demonstrated excitatory GABA signaling, remained synaptically active, and facilitated network activity as assayed by the frequency of extracellular action potentials and spontaneous network-driven oscillations. These data support a more inhibitory role for GABA in the unperturbed immature brain, demonstrate the utility of the acute brain slice preparation for the study of the consequences of trauma, and provide potential mechanisms for both GABA-mediated excitatory network events in the slice preparation and early post-traumatic seizures. PMID:22442068
What's Special about the Ethical Challenges of Studying Disorders with Altered Brain Activity?
Cassaday, Helen J
Where there is no viable alternative, studies of neuronal activity are conducted on animals. The use of animals, particularly for invasive studies of the brain, raises a number of ethical issues. Practical or normative ethics are enforced by legislation, in relation to the dominant welfare guidelines developed in the United Kingdom and elsewhere. Guidelines have typically been devised to cover all areas of biomedical research using animals in general, and thus lack any specific focus on neuroscience studies at the level of the ethics, although details of the specific welfare recommendations are different for invasive studies of the brain. Ethically, there is no necessary distinction between neuroscience and other biomedical research in that the brain is a final common path for suffering, irrespective of whether this involves any direct experience of pain. One exception arises in the case of in vitro studies, which are normally considered as an acceptable replacement for in vivo studies. However, to the extent sentience is possible, maintaining central nervous system tissue outside the body naturally raises ethical questions. Perhaps the most intractable challenge to the ethical use of animals in order to model neuronal disorder is presented by the logical impasse in the argument that the animal is similar enough to justify the validity of the experimental model, but sufficiently different in sentience and capacity for suffering, for the necessary experimental procedures to be permissible. PMID:25205325
Altered cognition-related brain activity and interactions with acute pain in migraine
Mathur, Vani A.; Khan, Shariq A.; Keaser, Michael L.; Hubbard, Catherine S.; Goyal, Madhav; Seminowicz, David A.
Little is known about the effect of migraine on neural cognitive networks. However, cognitive dysfunction is increasingly being recognized as a comorbidity of chronic pain. Pain appears to affect cognitive ability and the function of cognitive networks over time, and decrements in cognitive function can exacerbate affective and sensory components of pain. We investigated differences in cognitive processing and pain–cognition interactions between 14 migraine patients and 14 matched healthy controls using an fMRI block-design with two levels of task difficulty and concurrent heat (painful and not painful) stimuli. Across groups, cognitive networks were recruited in response to a difficult cognitive task, and a pain–task interaction was found in the right (contralateral to pain stimulus) posterior insula (pINS), such that activity was modulated by decreasing the thermal pain stimulus or by engaging the difficult cognitive task. Migraine patients had less task-related deactivation within the left dorsolateral prefrontal cortex (DLPFC) and left dorsal anterior midcingulate cortex (aMCC) compared to controls. These regions have been reported to have decreased cortical thickness and cognitive-related deactivation within other pain populations, and are also associated with pain regulation, suggesting that the current findings may reflect altered cognitive function and top-down regulation of pain. During pain conditions, patients had decreased task-related activity, but more widespread task-related reductions in pain-related activity, compared to controls, suggesting cognitive resources may be diverted from task-related to pain-reduction-related processes in migraine. Overall, these findings suggest that migraine is associated with altered cognitive-related neural activity, which may reflect altered pain regulatory processes as well as broader functional restructuring. PMID:25610798
Alterations in Hippocampal Network Activity after In Vitro Traumatic Brain Injury.
Kang, Woo Hyeun; Cao, Wenzhe; Graudejus, Oliver; Patel, Tapan P; Wagner, Sigurd; Meaney, David F; Morrison, Barclay
Traumatic brain injury (TBI) alters function and behavior, which can be characterized by changes in electrophysiological function in vitro. A common cognitive deficit after mild-to-moderate TBI is disruption of persistent working memory, of which the in vitro correlate is long-lasting, neuronal network synchronization that can be induced pharmacologically by the gamma-aminobutyric acid A antagonist, bicuculline. We utilized a novel in vitro platform for TBI research, the stretchable microelectrode array (SMEA), to investigate the effects of TBI on bicuculline-induced, long-lasting network synchronization in the hippocampus. Mechanical stimulation significantly disrupted bicuculline-induced, long-lasting network synchronization 24?h after injury, despite the continued ability of the injured neurons to fire, as revealed by a significant increase in the normalized spontaneous event rate in the dentate gyrus (DG) and CA1. A second challenge with bicuculline 24?h after the first challenge significantly decreased the normalized spontaneous event rate in the DG. In addition, we illustrate the utility of the SMEA for TBI research by combining multiple experimental paradigms in one platform, which has the potential to enable novel investigations into the mechanisms responsible for functional consequences of TBI and speed the rate of drug discovery. PMID:25517970
Prenatal drug exposure to illicit drugs alters working memory-related brain activity and underlying network properties in adolescence.
Schweitzer, Julie B; Riggins, Tracy; Liang, Xia; Gallen, Courtney; Kurup, Pradeep K; Ross, Thomas J; Black, Maureen M; Nair, Prasanna; Salmeron, Betty Jo
The persistence of effects of prenatal drug exposure (PDE) on brain functioning during adolescence is poorly understood. We explored neural activation to a visuospatial working memory (VSWM) versus a control task using functional magnetic resonance imaging (fMRI) in adolescents with PDE and a community comparison group (CC) of non-exposed adolescents. We applied graph theory metrics to resting state data using a network of nodes derived from the VSWM task activation map to further explore connectivity underlying WM functioning. Participants (ages 12-15 years) included 47 adolescents (27 PDE and 20 CC). All analyses controlled for potentially confounding differences in birth characteristics and postnatal environment. Significant group by task differences in brain activation emerged in the left middle frontal gyrus (BA 6) with the CC group, but not the PDE group, activating this region during VSWM. The PDE group deactivated the culmen, whereas the CC group activated it during the VSWM task. The CC group demonstrated a significant relation between reaction time and culmen activation, not present in the PDE group. The network analysis underlying VSWM performance showed that PDE group had lower global efficiency than the CC group and a trend level reduction in local efficiency. The network node corresponding to the BA 6 group by task interaction showed reduced nodal efficiency and fewer direct connections to other nodes in the network. These results suggest that adolescence reveals altered neural functioning related to response planning that may reflect less efficient network functioning in youth with PDE. PMID:25683798
Altered temporal variance and neural synchronization of spontaneous brain activity in anesthesia.
Huang, Zirui; Wang, Zhiyao; Zhang, Jianfeng; Dai, Rui; Wu, Jinsong; Li, Yuan; Liang, Weimin; Mao, Ying; Yang, Zhong; Holland, Giles; Zhang, Jun; Northoff, Georg
Recent studies at the cellular and regional levels have pointed out the multifaceted importance of neural synchronization and temporal variance of neural activity. For example, neural synchronization and temporal variance has been shown by us to be altered in patients in the vegetative state (VS). This finding nonetheless leaves open the question of whether these abnormalities are specific to VS or rather more generally related to the absence of consciousness. The aim of our study was to investigate the changes of inter- and intra-regional neural synchronization and temporal variance of resting state activity in anesthetic-induced unconsciousness state. Applying an intra-subject design, we compared resting state activity in functional magnetic resonance imaging (fMRI) between awake versus anesthetized states in the same subjects. Replicating previous studies, we observed reduced functional connectivity within the default mode network (DMN) and thalamocortical network in the anesthetized state. Importantly, intra-regional synchronization as measured by regional homogeneity (ReHo) and temporal variance as measured by standard deviation (SD) of the BOLD signal were significantly reduced in especially the cortical midline regions, while increased in the lateral cortical areas in the anesthetized state. We further found significant frequency-dependent effects of SD in the thalamus, which showed abnormally high SD in Slow-5 (0.01-0.027 Hz) in the anesthetized state. Our results show for the first time of altered temporal variance of resting state activity in anesthesia. Combined with our findings in the vegetative state, these findings suggest a close relationship between temporal variance, neural synchronization and consciousness. PMID:24867379
Altered Resting-State Brain Activity and Connectivity in Depressed Parkinson's Disease
Li, Erfeng; Liu, Jiajia; Yuan, Yonggui; Liu, Weiguo; Liu, Yijun
Depressive symptoms are common in Parkinson's disease (PD), but the neurophysiological mechanisms of depression in PD are poorly understood. The current study attempted to examine disrupted spontaneous local brain activities and functional connectivities that underlie the depression in PD. We recruited a total of 20 depressed PD patients (DPD), 40 non-depressed PD patients (NDPD) and 43 matched healthy controls (HC). All the subjects underwent neuropsychological tests and resting-state fMRI scanning. The between-group differences in the amplitude of low frequency fluctuations (ALFF) of BOLD signals were examined using post-hoc tests after the analysis of covariance. Compared with the NDPD and HC, the DPD group showed significantly increased ALFF in the left median cingulated cortex (MCC). The functional connectivity (FC) between left MCC and all the other voxels in the brain were then calculated. Compared with the HC and NDPD group, the DPD patients showed stronger FC between the left MCC and some of the major nodes of the default mode network (DMN), including the post cingulated cortex/precuneus, medial prefrontal cortex, inferior frontal gyrus, and cerebellum. Correlation analysis revealed that both the ALFF values in the left MCC and the FC between the left MCC and the nodes of DMN were significantly correlated with the Hamilton Depression Rating Scale score. Moreover, higher local activities in the left MCC were associated with increased functional connections between the MCC and the nodes of DMN in PD. These abnormal activities and connectivities of the limbic-cortical circuit may indicate impaired high-order cortical control or uncontrol of negative mood in DPD, which suggested a possible neural mechanism of the depression in PD. PMID:26147571
Diet fat alters synaptosomal phosphatidylethanolaminemethyl-transferase activity and phosphatidylcholine synthesis in brain
Hargreaves, K.M.; Clandinin, M.T.
Phosphatidylcholine (PC) can be synthesized via three routes, each having potentially different metabolic fates. One route for PC synthesis is methylation of phosphatidylethanolamine (PE). To examine if dietary fat affects membrane PE composition and phosphatidylethanolaminemethyltransferase (PEMT) activity, male weanling rats were fed semi-purified diets containing 20% (w/w) fat of differing fatty acid composition for 24 days. Microsomal and synaptic plasma membranes were isolated and phospholipid composition analyzed. PEMT activity was measured by incorporation of the methyl group from /sup 3/H-S-adenosylmethionine into PE. Polyunsaturated diets high in omega 6 fatty acids produce a high ratio of omega 6/omega 3 fatty acids in synaptic plasma membranes. Dietary omega 3 and omega 6 fatty acid levels are reflected in membrane phospholipid content of 22:6(3), 20:4(6), 22:4(6) and 22:5(6). Diet-induced increase in these longer chain homologues of omega 6 and omega 3 fatty acids and a high ratio of omega 6/omega 3 fatty acids in PE are both associated with increased PEMT activity. These results suggest that diet-fat induced change in fatty acid composition of membrane PE results in transition in PEMT activity and synthesis of PC in brain, by providing preferred species of PE for methylation.
Altered relationships between age and functional brain activation in adolescents at clinical high risk for psychosis.
Karlsgodt, Katherine H; van Erp, Theo G M; Bearden, Carrie E; Cannon, Tyrone D
Schizophrenia is considered a neurodevelopmental disorder, but whether the adolescent period, proximal to onset, is associated with aberrant development in individuals at clinical high risk (CHR) for psychosis is incompletely understood. While abnormal gray and white matter development has been observed, alterations in functional neuroimaging (fMRI) parameters during adolescence as related to conversion to psychosis have not yet been investigated. Twenty CHR individuals and 19 typically developing controls (TDC), (ages 14-21), were recruited from the Center for Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants performed a Sternberg-style verbal working memory (WMem) task during fMRI and data were analyzed using a cross-sectional design to test the hypothesis that there is a deviant developmental trajectory in WMem associated neural circuitry in those at risk for psychosis. Eight of the CHR adolescents converted to psychosis within 2 years of initial assessment. A voxel-wise regression examining the relationship between age and activation revealed a significant group-by-age interaction. TDC showed a negative association between age and functional activation in the WMem circuitry while CHR adolescents showed a positive association. Moreover, CHR patients who later converted to overt psychosis showed a distinct pattern of abnormal age-associated activation in the frontal cortex relative to controls, while non-converters showed a more diffuse posterior pattern. Finding that age related variation in baseline patterns of neural activity differentiate individuals who subsequently convert to psychosis from healthy subjects suggests that these differences are likely to be clinically relevant. PMID:24144510
Prenatal ethanol exposure alters ethanol-induced Fos immunoreactivity and dopaminergic activity in the mesocorticolimbic pathway of the adolescent brain.
Fabio, M C; Vivas, L M; Pautassi, R M
Prenatal ethanol exposure (PEE) promotes alcohol intake during adolescence, as shown in clinical and pre-clinical animal models. The mechanisms underlying this effect of prenatal ethanol exposure on postnatal ethanol intake remain, however, mostly unknown. Few studies assessed the effects of moderate doses of prenatal ethanol on spontaneous and ethanol-induced brain activity on adolescence. This study measured, in adolescent (female) Wistar rats prenatally exposed to ethanol (0.0 or 2.0g/kg/day, gestational days 17-20) or non-manipulated (NM group) throughout pregnancy, baseline and ethanol-induced cathecolaminergic activity (i.e., colocalization of c-Fos and tyrosine hydroxylase) in ventral tegmental area (VTA), and baseline and ethanol-induced Fos immunoreactivity (ir) in nucleus accumbens shell and core (AcbSh and AcbC, respectively) and prelimbic (PrL) and infralimbic (IL) prefrontal cortex. The rats were challenged with ethanol (dose: 0.0, 1.25, 2.5 or 3.25g/kg, i.p.) at postnatal day 37. Rats exposed to vehicle prenatally (VE group) exhibited reduced baseline dopaminergic tone in VTA; an effect that was inhibited by prenatal ethanol exposure (PEE group). Dopaminergic activity in VTA after the postnatal ethanol challenge was greater in PEE than in VE or NM animals. Ethanol-induced Fos-ir at AcbSh was found after 1.25g/kg and 2.5g/kg ethanol, in VE and PEE rats, respectively. PEE did not alter ethanol-induced Fos-ir at IL but reduced ethanol-induced Fos-ir at PrL. These results suggest that prenatal ethanol exposure heightens dopaminergic activity in the VTA and alters the response of the mesocorticolimbic pathway to postnatal ethanol exposure. These effects may underlie the enhanced vulnerability to develop alcohol-use disorders of adolescents with a history of in utero ethanol exposure. PMID:26057446
fMRI-acoustic noise alters brain activation during working memory tasks
D. Tomasi; E. C. Caparelli; L. Chang; T. Ernst
Scanner noise during functional magnetic resonance imaging (fMRI) may interfere with brain function and change blood oxygenation level dependent (BOLD) signals, a problem that generally worsens at the higher field strengths. Therefore, we studied the effect of increased acoustic noise on fMRI during verbal working memory (WM) processing. The sound pressure level of scanner noise was increased by 12 dBA
HIV-1 induces cytoskeletal alterations and Rac1 activation during monocyte-blood–brain barrier interactions: modulatory role of CCR5
Background Most HIV strains that enter the brain are macrophage-tropic and use the CCR5 receptor to bind and infect target cells. Because the cytoskeleton is a network of protein filaments involved in cellular movement and migration, we investigated whether CCR5 and the cytoskeleton are involved in endothelial-mononuclear phagocytes interactions, adhesion, and HIV-1 infection. Results Using a cytoskeleton phospho-antibody microarray, we showed that after co-culture with human brain microvascular endothelial cells (HBMEC), HIV-1 infected monocytes increased expression and activation of cytoskeleton-associated proteins, including Rac1/cdc42 and cortactin, compared to non-infected monocytes co-cultured with HBMEC. Analysis of brain tissues from HIV-1-infected patients validated these findings, and showed transcriptional upregulation of Rac1 and cortactin, as well as increased activation of Rac1 in brain tissues of HIV-1-infected humans, compared to seronegative individuals and subjects with HIV-1-encephalitis. Confocal imaging showed that brain cells expressing phosphorylated Rac1 were mostly macrophages and blood vessels. CCR5 antagonists TAK-799 and maraviroc prevented HIV-induced upregulation and phosphorylation of cytoskeleton-associated proteins, prevented HIV-1 infection of macrophages, and diminished viral-induced adhesion of monocytes to HBMEC. Ingenuity pathway analysis suggests that during monocyte-endothelial interactions, HIV-1 alters protein expression and phosphorylation associated with integrin signaling, cellular morphology and cell movement, cellular assembly and organization, and post-translational modifications in monocytes. CCR5 antagonists prevented these HIV-1-induced alterations. Conclusions HIV-1 activates cytoskeletal proteins during monocyte-endothelial interactions and increase transcription and activation of Rac1 in brain tissues. In addition to preventing macrophage infection, CCR5 antagonists could diminish viral-induced alteration and phosphorylation of cytoskeletal proteins, monocyte adhesion to the brain endothelium and viral entry into the central nervous system. PMID:24571616
Distinct mechanisms of altered brain activation in patients with multiple sclerosis
Katrin Morgen; Gebhard Sammer; Susan M. Courtney; Tobias Wolters; Hanne Melchior; Carlo R. Blecker; Patrick Oschmann; Manfred Kaps; Dieter Vaitl
Cerebral reorganization may limit the effects of central nervous system tissue damage on cognition in patients with multiple sclerosis (MS). This study investigated fMRI activation patterns in patients with relapsing-remitting MS and healthy control subjects during performance of a delayed recognition task. As intended, fMRI task performance was similar in the MS and the control group, whereas neuropsychological testing revealed
Prevention of haloperidol-induced alterations in brain acetylcholinesterase activity by vitamins B co-administration in a rodent model of tardive dyskinesia.
de Oliveira, Gersilene Valente; Gomes, Patrícia Xavier Lima; de Araújo, Fernanda Yvelize Ramos; Vasconcelos, Silvânia Maria Mendes; Júnior, Hélio Vitoriano Nobre; de Sousa, Francisca Cléa Florenço; de Lucena, David F; Hyphantis, Thomas N; Carvalho, André Férrer; Macędo, Danielle Silveira
Tardive dyskinesia (TD) is an iatrogenic syndrome being a significant adverse outcome of typical and atypical antipsychotic therapy. Recently we demonstrated that vitamins B (B1, B6, B12 alone or in combination) were able to prevent haloperidol-induced orofacial dyskinesia (OD) possibly by their antioxidant activity in the striatum, using a well-established model of TD. Here, based on the fact that alterations in cholinergic neurotransmission are related to TD pathophysiology and that vitamins B seems to influence brain cholinergic neurotransmission, we decided to investigate the effects of vitamins B1, B6, B12 and their association, vitamin B cocktail in haloperidol-induced cholinergic alterations, evaluated by alterations in acetylcholinesterase (AChE) activity, in striatum, prefrontal cortex and hippocampus, as a way to determine the participation of cholinergic neurotransmission, in these vitamins antidyskinetic mechanism. Haloperidol 1 mg/kg?i.p. daily administration during 21 days to Wistar rats caused OD while decreased AChE activity in all brain areas studied. Vitamins B administration (B1:B6:B12 at 60:60:0.6 mg/kg, s.c) alone and vitamin B cocktail co-administered with haloperidol prevented OD development and increased AChE activity in all brain areas studied, with the maximum activity increment observed in the hippocampus of the animals co-treated with vitamin B12 and vitamin B cocktail. The antidyskinetic drug, clozapine did not induce OD and increased AChE activity similarly to the groups coadministered with vitamin B and HAL. The present data suggest that vitamins B can prevent haloperidol-induced alterations in AChE activity what can be related to the mechanism underlying their antidyskinetic effect. PMID:23095989
Hypersexuality or altered sexual preference following brain injury
B L Miller; J L Cummings; H McIntyre; G Ebers; M Grode
Eight patients are described in whom either hypersexuality (four cases) or change in sexual preference (four cases) occurred following brain injury. In this series disinhibition of sexual activity and hypersexuality followed medial basal-frontal or diencephalic injury. This contrasted with the patients demonstrating altered sexual preference whose injuries involved limbic system structures. In some patients altered sexual behaviour may be the
A novel fMRI paradigm suggests that pedaling-related brain activation is altered after stroke
Promjunyakul, Nutta-on; Schmit, Brian D.; Schindler-Ivens, Sheila M.
The purpose of this study was to examine the feasibility of using functional magnetic resonance imaging (fMRI) to measure pedaling-related brain activation in individuals with stroke and age-matched controls. We also sought to identify stroke-related changes in brain activation associated with pedaling. Fourteen stroke and 12 control subjects were asked to pedal a custom, MRI-compatible device during fMRI. Subjects also performed lower limb tapping to localize brain regions involved in lower limb movement. All stroke and control subjects were able to pedal while positioned for fMRI. Two control subjects were withdrawn due to claustrophobia, and one control data set was excluded from analysis due to an incidental finding. In the stroke group, one subject was unable to enter the gantry due to excess adiposity, and one stroke data set was excluded from analysis due to excessive head motion. Consequently, 81% of subjects (12/14 stroke, 9/12 control) completed all procedures and provided valid pedaling-related fMRI data. In these subjects, head motion was ?3 mm. In both groups, brain activation localized to the medial aspect of M1, S1, and Brodmann's area 6 (BA6) and to the cerebellum (vermis, lobules IV, V, VIII). The location of brain activation was consistent with leg areas. Pedaling-related brain activation was apparent on both sides of the brain, with values for laterality index (LI) of –0.06 (0.20) in the stroke cortex, 0.05 (±0.06) in the control cortex, 0.29 (0.33) in the stroke cerebellum, and 0.04 (0.15) in the control cerebellum. In the stroke group, activation in the cerebellum – but not cortex – was significantly lateralized toward the damaged side of the brain (p = 0.01). The volume of pedaling-related brain activation was smaller in stroke as compared to control subjects. Differences reached statistical significance when all active regions were examined together [p = 0.03; 27,694 (9,608) ?L stroke; 37,819 (9,169) ?L control]. When individual regions were examined separately, reduced brain activation volume reached statistical significance in BA6 [p = 0.04; 4,350 (2,347) ?L stroke; 6,938 (3,134) ?L control] and cerebellum [p = 0.001; 4,591 (1,757) ?L stroke; 8,381 (2,835) ?L control]. Regardless of whether activated regions were examined together or separately, there were no significant between-group differences in brain activation intensity [p = 0.17; 1.30 (0.25)% stroke; 1.16 (0.20)% control]. Reduced volume in the stroke group was not observed during lower limb tapping and could not be fully attributed to differences in head motion or movement rate. There was a tendency for pedaling-related brain activation volume to increase with increasing work performed by the paretic limb during pedaling (p = 0.08, r = 0.525). Hence, the results of this study provide two original and important contributions. First, we demonstrated that pedaling can be used with fMRI to examine brain activation associated with lower limb movement in people with stroke. Unlike previous lower limb movements examined with fMRI, pedaling involves continuous, reciprocal, multijoint movement of both limbs. In this respect, pedaling has many characteristics of functional lower limb movements, such as walking. Thus, the importance of our contribution lies in the establishment of a novel paradigm that can be used to understand how the brain adapts to stroke to produce functional lower limb movements. Second, preliminary observations suggest that brain activation volume is reduced during pedaling post-stroke. Reduced brain activation volume may be due to anatomic, physiology, and/or behavioral differences between groups, but methodological issues cannot be excluded. Importantly, brain action volume post-stroke was both task-dependent and mutable, which suggests that it could be modified through rehabilitation. Future work will explore these possibilities. PMID:26089789
Functional Alterations in Brain Activation and Deactivation in Mild Cognitive Impairment in Response to a Graded Working Memory Challenge
N. A. Kochan; M. Breakspear; M. J. Slavin; M. Valenzuela; S. McCraw; H. Brodaty; P. S. Sachdev
Aim: To investigate dynamic changes in functional brain activity in mild cognitive impairment (MCI) in response to a graded working memory (WM) challenge with increasing memory load. Methods: In an event-related functional magnetic resonance imaging (fMRI) study, 35 MCI and 22 cognitively normal subjects performed a visuospatial associative WM task with 3 load levels. Potential performance differences were controlled for
Altered arginine metabolism in Alzheimer's disease brains.
Liu, Ping; Fleete, Michael S; Jing, Yu; Collie, Nicola D; Curtis, Maurice A; Waldvogel, Henry J; Faull, Richard L M; Abraham, Wickliffe C; Zhang, Hu
L-arginine is a semi-essential amino acid with a number of bioactive metabolites. Accumulating evidence suggests the implication of altered arginine metabolism in the pathogenesis of Alzheimer's disease (AD). The present study systematically compared the metabolic profile of L-arginine in the superior frontal gyrus, hippocampus, and cerebellum from AD (mean age 80 years) and normal (mean age 80 or 60 years) cases. The activity and protein expression of nitric oxide synthase and arginase were altered with AD and age in a region-specific manner. There were also AD- and age-related changes in the tissue concentrations of L-arginine and its downstream metabolites (L-citrulline, L-ornithine, agmatine, putrescine, spermidine, spermine, glutamate, ?-aminobutyric acid, and glutamine) in a metabolite- or region-specific manner. These findings demonstrate that arginine metabolism is dramatically altered in diverse regions of AD brains, thus meriting further investigation to understand its role in the pathogenesis and/or progression of the disease. PMID:24746363
Source-based neurofeedback methods using EEG recordings: training altered brain activity in a functional brain source derived from blind source separation
White, David J.; Congedo, Marco; Ciorciari, Joseph
A developing literature explores the use of neurofeedback in the treatment of a range of clinical conditions, particularly ADHD and epilepsy, whilst neurofeedback also provides an experimental tool for studying the functional significance of endogenous brain activity. A critical component of any neurofeedback method is the underlying physiological signal which forms the basis for the feedback. While the past decade has seen the emergence of fMRI-based protocols training spatially confined BOLD activity, traditional neurofeedback has utilized a small number of electrode sites on the scalp. As scalp EEG at a given electrode site reflects a linear mixture of activity from multiple brain sources and artifacts, efforts to successfully acquire some level of control over the signal may be confounded by these extraneous sources. Further, in the event of successful training, these traditional neurofeedback methods are likely influencing multiple brain regions and processes. The present work describes the use of source-based signal processing methods in EEG neurofeedback. The feasibility and potential utility of such methods were explored in an experiment training increased theta oscillatory activity in a source derived from Blind Source Separation (BSS) of EEG data obtained during completion of a complex cognitive task (spatial navigation). Learned increases in theta activity were observed in two of the four participants to complete 20 sessions of neurofeedback targeting this individually defined functional brain source. Source-based EEG neurofeedback methods using BSS may offer important advantages over traditional neurofeedback, by targeting the desired physiological signal in a more functionally and spatially specific manner. Having provided preliminary evidence of the feasibility of these methods, future work may study a range of clinically and experimentally relevant brain processes where individual brain sources may be targeted by source-based EEG neurofeedback. PMID:25374520
Exercise Improves Executive Function and Achievement and Alters Brain Activation in Overweight Children: A Randomized Controlled Trial
Davis, Catherine L.; Tomporowski, Phillip D.; McDowell, Jennifer E.; Austin, Benjamin P.; Miller, Patricia H.; Yanasak, Nathan E.; Allison, Jerry D.; Naglieri, Jack A.
Objective This experiment tested the hypothesis that exercise would improve executive function. Design Sedentary, overweight 7- to 11-year-old children (N = 171, 56% female, 61% Black, M ± SD age 9.3 ± 1.0 yrs, body mass index (BMI) 26 ± 4.6 kg/m2, BMI z-score 2.1 ± 0.4) were randomized to 13 ± 1.6 weeks of an exercise program (20 or 40 minutes/day), or a control condition. Main outcome measures Blinded, standardized psychological evaluations (Cognitive Assessment System and Woodcock-Johnson Tests of Achievement III) assessed cognition and academic achievement. Functional magnetic resonance imaging measured brain activity during executive function tasks. Results Intent to treat analysis revealed dose response benefits of exercise on executive function and mathematics achievement. Preliminary evidence of increased bilateral prefrontal cortex activity and reduced bilateral posterior parietal cortex activity due to exercise was also observed. Conclusion Consistent with results obtained in older adults, a specific improvement on executive function and brain activation changes due to exercise were observed. The cognitive and achievement results add evidence of dose response, and extend experimental evidence into childhood. This study provides information on an educational outcome. Besides its importance for maintaining weight and reducing health risks during a childhood obesity epidemic, physical activity may prove to be a simple, important method of enhancing aspects of children's mental functioning that are central to cognitive development. This information may persuade educators to implement vigorous physical activity. PMID:21299297
Carbofuran induced oxidative stress mediated alterations in Na?-K?-ATPase activity in rat brain: amelioration by vitamin E.
Jaiswal, Sunil Kumar; Siddiqi, Nikhat Jamal; Sharma, Bechan
Pesticides cause oxidative stress and adversely influence Na(+)-K(+)-ATPase activity in animals. Since impact of carbofuran has not been properly studied in the mammalian brain, the ability of carbofuran to induce oxidative stress and modulation in Na(+)-K(+)-ATPase activity and its amelioration by vitamin E was performed. The rats divided into six groups received two different doses of carbofuran (15% and 30% LD50) for 15 days. The results suggested that the carbofuran treatment caused a significant elevation in levels of malonaldehyde and reduced glutathione and sharp inhibition in the activities of super oxide dismutase, catalase, and glutathione-S-transferase; the effect being dose dependent. Carbofuran at different doses also caused sharp reduction in the activity of Na(+)-K(+)-ATPase. The pretreatment of vitamin E, however, showed a significant recovery in these indices. The pretreatment of rats with vitamin E offered protection from carbofuran-induced oxidative stress. PMID:24865641
Altered brain activation during response inhibition and error processing in subjects with Internet gaming disorder: a functional magnetic imaging study.
Ko, Chih-Hung; Hsieh, Tsyh-Jyi; Chen, Chiao-Yun; Yen, Cheng-Fang; Chen, Cheng-Sheng; Yen, Ju-Yu; Wang, Peng-Wei; Liu, Gin-Chung
The aim of the present study was to evaluate the impulsivity and brain correlates of response inhibition and error processing among subjects with Internet gaming disorder (IGD). We evaluated the response inhibition and error processing by functional magnetic resonance imaging (fMRI) in subjects with IGD and controls. Twenty-six men with IGD for at least 2 years and 23 controls with no history of IGD were recruited as the IGD and control groups, respectively. All subjects performed the event-related designed Go/No-go task under fMRI and completed questionnaires related to Internet addiction and impulsivity. The IGD group exhibited a higher score for impulsivity than the control group. The IGD group also exhibited higher brain activation when processing response inhibition over the left orbital frontal lobe and bilateral caudate nucleus than controls. Both the IGD and control groups exhibited activation of the insula and anterior cingulate cortex during error processing. The activation over the right insula was lower in the subjects with IGD than the control group. Our results support the fact that the fronto-striatal network involved in response inhibition, and the salience network, anchored by the anterior cingulate and insula, contributes to error processing. Further, adults with IGD have impaired insular function in error processing and greater activation of the fronto-striatal network in order to maintain their response inhibition performance. PMID:24469099
Brain alterations in paedophilia: a critical review.
Mohnke, Sebastian; Müller, Sabine; Amelung, Till; Krüger, Tillmann H C; Ponseti, Jorge; Schiffer, Boris; Walter, Martin; Beier, Klaus M; Walter, Henrik
Psychosocial and biological factors have been implicated in paedophilia, such as alterations in brain structure and function. The purpose of this paper is to review the expanding body of literature on this topic including brain abnormality case reports, as well as structural and functional neuroimaging studies. Case studies of men who have committed sexual offences against children implicate frontal and temporal abnormalities that may be associated with impaired impulse inhibition. Structural neuroimaging investigations show volume reductions in paedophilic men. Although the findings have been heterogeneous, smaller amygdala volume has been replicated repeatedly. Functional neuroimaging investigations demonstrate an overlap between paedophiles and teleiophiles during sexual arousal processing. While it is controversial among studies regarding group differences, reliable discrimination between paedophilic and teleiophilic men may be achieved using functional activation patterns. Nevertheless, the heterogeneous findings published so far suggest further research is necessary to disentangle the neurobiological mechanisms of paedophilic preference. A number of methodological confounds have been identified, which may account for the inconsistent results that could prove to be beneficial for future investigations. PMID:25116710
Altered brain functional networks in heavy smokers.
Lin, Fuchun; Wu, Guangyao; Zhu, Ling; Lei, Hao
Recent neuroimaging studies have demonstrated that cigarette smoking is associated with changed brain structure and function. However, little is known about alterations of the topological organization of brain functional networks in heavy smokers. Thirty-one heavy smokers and 33 non-smokers underwent a resting-state functional magnetic resonance imaging scan. The whole-brain functional networks were constructed by thresholding the correlation matrices of 90 brain regions and their topological properties were analyzed using graph network analysis. Non-parametric permutation tests were performed to investigate group differences in network topological measures and multiple regression analysis was conducted to determine the relationships between the network metrics and smoking-related variables. Both heavy smokers and non-smokers exhibited small-world architecture in their brain functional networks. Compared with non-smokers, however, heavy smokers showed altered topological measurements characterized by lower global efficiency, higher local efficiency and clustering coefficients and greater path length. Furthermore, heavy smokers demonstrated decreased nodal global efficiency mainly in brain regions within the default mode network, whereas increased nodal local efficiency predominated in the visual-related regions. In addition, heavy smokers exhibited an association between the altered network metrics and the duration of cigarette use or the severity of nicotine dependence. Our results suggest that heavy smokers may have less efficient network architecture in the brain, and chronic cigarette smoking is associated with disruptions in the topological organization of brain networks. Our findings may further the understanding of the effects of chronic cigarette smoking on the brain and the pathophysiological mechanisms underlying nicotine dependence. PMID:24962385
Activation Changes in Zebra Finch (Taeniopygia guttata) Brain Areas Evoked by Alterations of the Earth Magnetic Field
Keary, Nina; Bischof, Hans-Joachim
Many animals are able to perceive the earth magnetic field and to use it for orientation and navigation within the environment. The mechanisms underlying the perception and processing of magnetic field information within the brain have been thoroughly studied, especially in birds, but are still obscure. Three hypotheses are currently discussed, dealing with ferromagnetic particles in the beak of birds, with the same sort of particles within the lagena organs, or describing magnetically influenced radical-pair processes within retinal photopigments. Each hypothesis is related to a well-known sensory organ and claims parallel processing of magnetic field information with somatosensory, vestibular and visual input, respectively. Changes in activation within nuclei of the respective sensory systems have been shown previously. Most of these previous experiments employed intensity enhanced magnetic stimuli or lesions. We here exposed unrestrained zebra finches to either a stationary or a rotating magnetic field of the local intensity and inclination. C-Fos was used as an activity marker to examine whether the two treatments led to differences in fourteen brain areas including nuclei of the somatosensory, vestibular and visual system. An ANOVA revealed an overall effect of treatment, indicating that the magnetic field change was perceived by the birds. While the differences were too small to be significant in most areas, a significant enhancement of activation by the rotating stimulus was found in a hippocampal subdivision. Part of the hyperpallium showed a strong, nearly significant, increase. Our results are compatible with previous studies demonstrating an involvement of at least three different sensory systems in earth magnetic field perception and suggest that these systems, probably less elaborated, may also be found in nonmigrating birds. PMID:22679515
Heavy Metals and Epigenetic Alterations in Brain Tumors
Caffo, Maria; Caruso, Gerardo; Fata, Giuseppe La; Barresi, Valeria; Visalli, Maria; Venza, Mario; Venza, Isabella
Heavy metals and their derivatives can cause various diseases. Numerous studies have evaluated the possible link between exposure to heavy metals and various cancers. Recent data show a correlation between heavy metals and aberration of genetic and epigenetic patterns. From a literature search we noticed few experimental and epidemiological studies that evaluate a possible correlation between heavy metals and brain tumors. Gliomas arise due to genetic and epigenetic alterations of glial cells. Changes in gene expression result in the alteration of the cellular division process. Epigenetic alterations in brain tumors include the hypermethylation of CpG group, hypomethylation of specific genes, aberrant activation of genes, and changes in the position of various histones. Heavy metals are capable of generating reactive oxygen assumes that key functions in various pathological mechanisms. Alteration of homeostasis of metals could cause the overproduction of reactive oxygen species and induce DNA damage, lipid peroxidation, and alteration of proteins. In this study we summarize the possible correlation between heavy metals, epigenetic alterations and brain tumors. We report, moreover, the review of relevant literature. PMID:25646073
Behavioral stimulation without alteration of beta and 5-HT receptors and adenylate cyclase activity in rat brain after chronic sertraline administration.
Tadokoro, C; Kiuchi, Y; Yamazaki, Y; Nara, K; Oguchi, K; Kamijima, K
Effects of chronic treatment with selective 5-HT reuptake inhibitors (SSRIs) on the monoaminergic functions have not been much investigated in compared with tricyclic antidepressants. Therefore, we compared the effects of 3-week treatment with sertraline, a potent SSRI, to those of imipramine (10 mg/kg, IP, twice a day), on monoamine receptors and adenylate cyclase (AC) activity in rat brain. Two-week treatment with both sertraline and imipramine reduced immobility in the water wheel test to the comparable extent. Sertraline treatment did not affect Kd and Bmax of [3H]CGP12177 and [3H]ketanserin bindings or cAMP, accumulation by norepinephrine, isoproternol, 5'-guanylylimidodiphosphate [Gpp(NH)p] and forskolin in the cortical membrane compared with vehicle-treated rats. On the other hand, imipramine treatment decreased Bmax of both bindings and norepinephrine- or isoproternol-stimulated cAMP accumulation. Treatment with either antidepressant induced no apparent changes in [3H]8-OH-DPAT [2-(N, N-dipropylamino)-8-hydroxy-1,2,3,4-tetrahydronaphthalene] binding in the hippocampal membrane. These results suggested that chronic treatment of sertraline induced little effect on monoamine receptors and AC activity in the brain and that the alteration of these functions may not be primarily involved in antidepressive effects of antidepressants, at least of SSRIs. PMID:9106909
Platelets Potentiate Brain Endothelial Alterations Induced by Plasmodium falciparum
Samuel C. Wassmer; Valery Combes; Francisco J. Candal; Irene Juhan-Vague; Georges E. Grau
Brain lesions of cerebral malaria (CM) are characterized by a sequestration of Plasmodium falciparum- parasitized red blood cells (PRBC) and platelets within brain microvessels, as well as by blood-brain barrier (BBB) disruption. In the present study, we evaluated the possibility that PRBC and platelets induce functional alterations in brain endothelium. In a human brain endothelial cell line, named HBEC-5i, exhibiting
When "altering brain function" becomes "mind control"
Koivuniemi, Andrew; Otto, Kevin
Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS) technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. "Under what conditions does 'altering brain function' qualify as 'mind control'?" In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control. PMID:25352789
Manganese alters rat brain amino acids levels
Santos, Dinamene; Batoreu, M. Camila; Almeida, Isabel; Ramos, Ruben; Sidoryk-Wegrzynowicz, M.; Aschner, Michael; Marreilha dos Santos, A.P.
Manganese (Mn) is an essential element and it acts as a cofactor for a number of enzymatic reactions, including those involved in amino acid, lipid, protein and carbohydrate metabolism. Excessive exposure to Mn can lead to poisoning, characterized by psychiatric disturbances and an extrapyramidal disorder. Mn-induced neuronal degeneration is associated with alterations in amino acids metabolism. In the present study, we analyzed whole rat brain amino acid content subsequent to 4 or 8 intraperitoneal (ip) injections, with 25 mg MnCl2/kg/day, at 48-hour (h) intervals. We noted a significant increase in glycine brain levels after 4 or 8 Mn injections (p<0.05 and p<0.01, respectively) and arginine also after 4 or 8 injections (p<0.001). Significant increases were also noted in brain proline (p<0.01), cysteine (p<0.05), phenylalanine (p<0.01) and tyrosine (p<0.01) levels after 8 Mn injections vs. the control group. These findings suggest that Mn-induced alterations in amino acid levels secondary to Mn affect the neurochemical milieu. PMID:22971893
Fischer, Shannon G.; Ricci, Lesley A.; Melloni, Richard H.
Male Syrian hamsters (Mesocricetus auratus) treated with moderately high doses (5.0mg/kg/day) of anabolic/androgenic steroids (AAS) during adolescence (P27–P56) display highly escalated offensive aggression. The current study examined whether adolescent AAS-exposure influenced the immunohistochemical localization of phosphate-activated glutaminase (PAG), the rate-limiting enzyme in the synthesis of glutamate, a fast-acting neurotransmitter implicated in the modulation of aggression in various species and models of aggression, as well as glutamate receptor 1 subunit (GluR1). Hamsters were administered AAS during adolescence, scored for offensive aggression using the resident-intruder paradigm, and then examined for changes in PAG and GluR1 immunoreactivity in areas of the brain implicated in aggression control. When compared with sesame oil-treated control animals, aggressive AAS-treated hamsters displayed a significant increase in the number of PAG- and area density of GluR1- containing neurons in several notable aggression regions, although the differential pattern of expression did not appear to overlap across brain regions. Together, these results suggest that altered glutamate synthesis and GluR1 receptor expression in specific aggression areas may be involved in adolescent AAS-induced offensive aggression. PMID:17418431
Traumatic Alterations in Consciousness: Traumatic Brain Injury
Blyth, Brian J.; Bazarian, Jeffrey J.
Mild traumatic brain injury (mTBI) refers to the clinical condition of transient alteration of consciousness as a result of traumatic injury to the brain. The priority of emergency care is to identify and facilitate the treatment of rare but potentially life threatening intra-cranial injuries associated with mTBI through the judicious application of appropriate imaging studies and neurosurgical consultation. Although post-mTBI symptoms quickly and completely resolve in the vast majority of cases, a significant number of patients will complain of lasting problems that may cause significant disability. Simple and early interventions such as patient education and appropriate referral can reduce the likelihood of chronic symptoms. Although definitive evidence is lacking, mTBI is likely to be related to significant long-term sequelae such as Alzheimer's disease and other neurodegenerative processes. PMID:20709244
Can adverse neonatal experiences alter brain development and subsequent behavior?
Anand, K J; Scalzo, F M
Self-destructive behavior in current society promotes a search for psychobiological factors underlying this epidemic. Perinatal brain plasticity increases the vulnerability to early adverse experiences, thus leading to abnormal development and behavior. Although several epidemiological investigations have correlated perinatal and neonatal complications with abnormal adult behavior, our understanding of the underlying mechanisms remains rudimentary. Models of early experience, such as repetitive pain, sepsis, or maternal separation in rodents and other species have noted multiple alterations in the adult brain, correlated with specific behavioral phenotypes depending on the timing and nature of the insult. The mechanisms mediating such changes in the neonatal brain have remained largely unexplored. We propose that lack of N-methyl-D-aspartate (NMDA) receptor activity from maternal separation and sensory isolation leads to increased apoptosis in multiple areas of the immature brain. On the other hand, exposure to repetitive pain may cause excessive NMDA/excitatory amino acid activation resulting in excitotoxic damage to developing neurons. These changes promote two distinct behavioral phenotypes characterized by increased anxiety, altered pain sensitivity, stress disorders, hyperactivity/attention deficit disorder, leading to impaired social skills and patterns of self-destructive behavior. The clinical important of these mechanisms lies in the prevention of early insults, effective treatment of neonatal pain and stress, and perhaps the discovery of novel therapeutic approaches that limit neuronal excitotoxicity or apoptosis. PMID:10657682
Altered brain activation in dorsolateral prefrontal cortex in adolescents and young adults at genetic risk for schizophrenia: An fMRI study of working memory
Larry J. Seidman; Heidi W. Thermenos; Russell A. Poldrack; Nicole K. Peace; Jennifer K. Koch; Stephen V. Faraone; Ming T. Tsuang
ObjectiveAdult first-degree relatives of persons with schizophrenia carry elevated genetic risk for the illness, demonstrate working memory (WM) impairments, and manifest alterations in dorsolateral prefrontal cortical (DLPFC) function during WM. Because substantially less is known about these phenotypes in adolescent subjects we sought to demonstrate that young relatives of persons with schizophrenia manifest impaired WM and altered prefrontal activation.
Altered Brain Activation in Early Drug-Naive Parkinson's Disease during Heat Pain Stimuli: An fMRI Study
Tan, Ying; Tan, Juan; Cui, Wenjuan; He, Hui; Bin, Yi; Deng, Jiayan; Tan, Rui; Tan, Wenrong; Liu, Tao; Zeng, Nanlin; Xiao, Ruhui; Yao, Dezhong; Wang, Xiaoming
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by motor and nonmotor signs and symptoms. To date, many studies of PD have focused on its cardinal motor symptoms. To study the nonmotor signs of early PD, we investigated the reactions solicited by heat pain stimuli in early untreated PD patients without pain using fMRI. The activation patterns of contact heat stimuli (51°C) were assessed in 14 patients and 17 age- and sex-matched healthy controls. Patients with PD showed significant decreases in activation of the superior temporal gyrus (STG) and insula compared with controls. In addition, a significant relationship between activation of the insula and STG and the pain scores was observed in healthy controls but not in PD. This study provided further support that the insula and STG are important parts of the somatosensory circuitry recruited during the period of pain. The hypoactivity of the STG and insula in PD implied that functions including affective, cognitive, and sensory-discriminative processes, which are associated with the insula and STG, were disturbed. This finding supports the view that leaving early PD untreated could be tied directly to central nervous system dysfunction. PMID:25628915
Alteration of Interictal Brain Activity in Patients with Temporal Lobe Epilepsy in the Left Dominant Hemisphere: A Resting-State MEG Study
Zhu, Haitao; Zhu, Jinlong; Zhao, Tiezhu; Wu, Yong; Liu, Hongyi; Wu, Ting; Yang, Lu; Zou, Yuanjie; Zhang, Rui; Zheng, Gang
Resting MEG activities were compared between patients with left temporal lobe epilepsy (LTLE) and normal controls. Using SAMg2, the activities of MEG data were reconstructed and normalized. Significantly elevated SAMg2 signals were found in LTLE patients in the left temporal lobe and medial structures. Marked decreases of SAMg2 signals were found in the wide extratemporal lobe regions, such as the bilateral visual cortex. The study also demonstrated a positive correlation between the seizure frequency and brain activities of the abnormal regions after the multiple linear regression analysis. These results suggested that the aberrant brain activities not only were related to the epileptogenic zones, but also existed in other extratemporal regions in patients with LTLE. The activities of the aberrant regions could be further damaged with the increase of the seizure frequency. Our findings indicated that LTLE could be a multifocal disease, including complex epileptic networks and brain dysfunction networks. PMID:25136558
IL-6 mediated alterations on immobile behavior of rats in the forced swim test via ERK1/2 activation in specific brain regions.
Wu, Tung-Huan; Lin, Chih-Hung
Interleukin-6 (IL-6), a proinflammatory cytokine, is well known as a mediator in early stage inflammatory immune reactions. In recent years, accumulating evidence has shown that IL-6 is concomitant with the occurrence of major depression. However, the identification of the role of IL-6, as either an illness causation or immunotherapy in depression, remains to be further established. In the present study, 5-week old male Sprague-Dawley (SD) rats were used along with the forced swim test (FST) and pharmacological techniques. The data show that rats subjected to 3-day intra-amygdala or intra-hippocampus, but not intra-frontal cortex, IL-6 treatments manifested a significant increase in the immobility time (IMT) in the FST. In addition, there was no obvious difference in body temperature between normal and 3-day IL-6 treated rats. Conversely, the rats receiving 3-day intra-amygdala or intra-hippocampus IL-6 inhibitor treatment expressed a significant reduction in IMT in the FST. Moreover, the 3-day IL-6 treated rats treated with SL 327, a blood-brain barrier penetrating MEK inhibitor, prior to the FST showed a significant decrease in the IL-6 elevated IMT. In addition, the results in the Western blot analysis were in parallel with those in the behavioral tests. Taken together, the results show that the immobile behavior of rats in the FST could be modulated by IL-6 via the amygdala or the hippocampus. Furthermore, the Erk1/2 activation in the amygdala or hippocampus seemed to play a role in the IL-6 mediated immobile behavioural alterations of rats in the FST. PMID:18573547
Altered baseline brain activity in experts measured by amplitude of low frequency fluctuations (ALFF): a resting state fMRI study using expertise model of acupuncturists
Dong, Minghao; Li, Jun; Shi, Xinfa; Gao, Shudan; Fu, Shijun; Liu, Zongquan; Liang, Fanrong; Gong, Qiyong; Shi, Guangming; Tian, Jie
It is well established that expertise modulates evoked brain activity in response to specific stimuli. Recently, researchers have begun to investigate how expertise influences the resting brain. Among these studies, most focused on the connectivity features within/across regions, i.e., connectivity patterns/strength. However, little concern has been given to a more fundamental issue whether or not expertise modulates baseline brain activity. We investigated this question using amplitude of low-frequency (<0.08 Hz) fluctuation (ALFF) as the metric of brain activity and a novel expertise model, i.e., acupuncturists, due to their robust proficiency in tactile perception and emotion regulation. After the psychophysical and behavioral expertise screening procedure, 23 acupuncturists and 23 matched non-acupuncturists (NA) were enrolled. Our results explicated higher ALFF for acupuncturists in the left ventral medial prefrontal cortex (VMPFC) and the contralateral hand representation of the primary somatosensory area (SI) (corrected for multiple comparisons). Additionally, ALFF of VMPFC was negatively correlated with the outcomes of the emotion regulation task (corrected for multiple comparisons). We suggest that our study may reveal a novel connection between the neuroplasticity mechanism and resting state activity, which would upgrade our understanding of the central mechanism of learning. Furthermore, by showing that expertise can affect the baseline brain activity as indicated by ALFF, our findings may have profound implication for functional neuroimaging studies especially those involving expert models, in that difference in baseline brain activity may either smear the spatial pattern of activations for task data or introduce biased results into connectivity-based analysis for resting data. PMID:25852511
Inflammasome Activation by Altered Proteostasis*
Shin, Jin Na; Fattah, Elmoataz Abdel; Bhattacharya, Abhisek; Ko, Soyoung; Eissa, N. Tony
The association between altered proteostasis and inflammatory disorders has been increasingly recognized, but the underlying mechanisms are not well understood. In this study, we show that deficiency of either autophagy or sequestosome 1 (p62 or SQSTM) led to inflammasome hyperactivation in response to LPS and ATP in primary macrophages and in mice in vivo. Importantly, induction of protein misfolding by puromycin, thapsigargin, or geldanamycin resulted in inflammasome activation that was more pronounced in autophagy- or p62-deficient macrophages. Accumulation of misfolded proteins caused inflammasome activation by inducing generation of nonmitochondrial reactive oxygen species and lysosomal damage, leading to release of cathepsin B. Our results suggest that altered proteostasis results in inflammasome activation and thus provide mechanisms for the association of altered proteostasis with inflammatory disorders. PMID:24178293
Brain mechanisms of altered conscious states during epileptic seizures.
Cavanna, Andrea Eugenio; Monaco, Francesco
Impaired consciousness has long been considered the hallmark of epileptic seizures. Both generalized seizures and complex partial seizures are characterized by a multifaceted spectrum of altered conscious states, in terms of the general level of awareness and the subjective contents of consciousness. Complete loss of consciousness occurs when epileptic activity involves both cortical and subcortical structures, as in tonic-clonic seizures and absence seizures. Medial temporal lobe discharges can selectively impair experience in complex partial seizures (with affected responsiveness) and certain simple partial seizures (with unaffected responsiveness). Electrical stimulation of temporal lobe structures has been shown to evoke similar subjective experiences. Findings from neurophysiological and brain-imaging studies in epilepsy have now demonstrated that involvement of the bilateral thalamus and upper brainstem leads to selective impairment of frontoparietal association cortices and midline 'default mode' networks, which results in ictal loss of consciousness. The spread of epileptic discharges from the medial temporal lobe to the same subcortical structures can ultimately cause impairment in the level of consciousness in the late ictal and immediate postictal phase of complex partial seizures. This paper reviews novel insights into the brain mechanisms that underlie alterations of consciousness during epileptic seizures and the implications for clinical practice in terms of diagnosis and management. PMID:19488084
Altered Cognitive Control Activations after Moderate-to-Severe Traumatic Brain Injury and Their Relationship to Injury Severity and Everyday-Life Function.
Olsen, Alexander; Brunner, Jan Ferenc; Indredavik Evensen, Kari Anne; Finnanger, Torun Gangaune; Vik, Anne; Skandsen, Toril; Landrř, Nils Inge; Hĺberg, Asta Kristine
This study investigated how the neuronal underpinnings of both adaptive and stable cognitive control processes are affected by traumatic brain injury (TBI). Functional magnetic resonance imaging (fMRI) was undertaken in 62 survivors of moderate-to-severe TBI (>1 year after injury) and 68 healthy controls during performance of a continuous performance test adapted for use in a mixed block- and event-related design. Survivors of TBI demonstrated increased reliance on adaptive task control processes within an a priori core region for cognitive control in the medial frontal cortex. TBI survivors also had increased activations related to time-on-task effects during stable task-set maintenance in right inferior parietal and prefrontal cortices. Increased brain activations in TBI survivors had a dose-dependent linear positive relationship to injury severity and were negatively correlated with self-reported cognitive control problems in everyday-life situations. Results were adjusted for age, education, and fMRI task performance. In conclusion, evidence was provided that the neural underpinnings of adaptive and stable control processes are differently affected by TBI. Moreover, it was demonstrated that increased brain activations typically observed in survivors of TBI might represent injury-specific compensatory adaptations also utilized in everyday-life situations. PMID:24557637
Altered Cognitive Control Activations after Moderate-to-Severe Traumatic Brain Injury and Their Relationship to Injury Severity and Everyday-Life Function
Olsen, Alexander; Brunner, Jan Ferenc; Indredavik Evensen, Kari Anne; Finnanger, Torun Gangaune; Vik, Anne; Skandsen, Toril; Landrř, Nils Inge; Hĺberg, Asta Kristine
This study investigated how the neuronal underpinnings of both adaptive and stable cognitive control processes are affected by traumatic brain injury (TBI). Functional magnetic resonance imaging (fMRI) was undertaken in 62 survivors of moderate-to-severe TBI (>1 year after injury) and 68 healthy controls during performance of a continuous performance test adapted for use in a mixed block- and event-related design. Survivors of TBI demonstrated increased reliance on adaptive task control processes within an a priori core region for cognitive control in the medial frontal cortex. TBI survivors also had increased activations related to time-on-task effects during stable task-set maintenance in right inferior parietal and prefrontal cortices. Increased brain activations in TBI survivors had a dose-dependent linear positive relationship to injury severity and were negatively correlated with self-reported cognitive control problems in everyday-life situations. Results were adjusted for age, education, and fMRI task performance. In conclusion, evidence was provided that the neural underpinnings of adaptive and stable control processes are differently affected by TBI. Moreover, it was demonstrated that increased brain activations typically observed in survivors of TBI might represent injury-specific compensatory adaptations also utilized in everyday-life situations. PMID:24557637
Exposure in fetus of methylazoxymethanol in the rat alters brain neurotrophins' levels and brain cells' proliferation
Veronica Di Fausto; Marco Fiore; Luigi Aloe
Changes during gestation have been shown to induce brain maldevelopment associated with changes in neurotrophins as nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neuropsychiatric disorders in humans. A rat model of altered prenatal brain development resembling the onset of schizophrenia has been obtained by administering in fetus methylazoxymethanol (MAM) at gestational day 12 which impairs the growth
Statistical parametric mapping reveals regional alterations in cannabinoid CB1 receptor distribution and G-protein activation in the 3D reconstructed epileptic rat brain
Sayers, Katherine W.; Nguyen, Peter T.; Blair, Robert E.; Sim-Selley, Laura J.; DeLorenzo, Robert J.
Summary Purpose The endocannabinoid system is known to modulate seizure activity in several in vivo and in vitro models, and CB1-receptor activation is anticonvulsant in the rat pilocarpine model of acquired epilepsy (AE). In these epileptic rats, a unique redistribution of the CB1 receptor occurs within the hippocampus; however, an anatomically inclusive analysis of the effect of status epilepticus (SE)–induced AE on CB1 receptors has not been thoroughly evaluated. Therefore, statistical parametric mapping (SPM), a whole-brain unbiased approach, was used to study the long-term effect of pilocarpine-induced SE on CB1-receptor binding and G-protein activation in rats with AE. Methods Serial coronal sections from control and epileptic rats were cut at equal intervals throughout the neuraxis and processed for [3H]WIN55,212-2 (WIN) autoradiography, WIN-stimulated [35S]GTP?S autoradiography, and CB1-receptor immunohistochemistry (IHC). The autoradiographic techniques were evaluated with both region of interest (ROI) and SPM analyses. Key Findings In rats with AE, regionally specific increases in CB1-receptor binding and activity were detected in cortex, discrete thalamic nuclei, and other regions including caudate-putamen and septum, and confirmed by IHC. However, CB1 receptors were unaltered in several brain regions, including substantia nigra and cerebellum, and did not exhibit regional decreases in rats with AE. Significance This study provides the first comprehensive evaluation of the regional distribution of changes in CB1-receptor expression, binding, and G-protein activation in the rat pilocarpine model of AE. These regions may ultimately serve as targets for cannabinomimetic compounds or manipulation of the endocannabinoid system in epileptic brain. PMID:22509801
Hyaluronan Deficiency Due to Has3 Knock-Out Causes Altered Neuronal Activity and Seizures via Reduction in Brain Extracellular Space
Arranz, Amaia M.; Perkins, Katherine L.; Irie, Fumitoshi; Lewis, David P.; Hrabe, Jan; Xiao, Fanrong; Itano, Naoki; Kimata, Koji
Hyaluronan (HA), a large anionic polysaccharide (glycosaminoglycan), is a major constituent of the extracellular matrix of the adult brain. To address its function, we examined the neurophysiology of knock-out mice deficient in hyaluronan synthase (Has) genes. Here we report that these Has mutant mice are prone to epileptic seizures, and that in Has3?/? mice, this phenotype is likely derived from a reduction in the size of the brain extracellular space (ECS). Among the three Has knock-out models, namely Has3?/?, Has1?/?, and Has2CKO, the seizures were most prevalent in Has3?/? mice, which also showed the greatest HA reduction in the hippocampus. Electrophysiology in Has3?/? brain slices demonstrated spontaneous epileptiform activity in CA1 pyramidal neurons, while histological analysis revealed an increase in cell packing in the CA1 stratum pyramidale. Imaging of the diffusion of a fluorescent marker revealed that the transit of molecules through the ECS of this layer was reduced. Quantitative analysis of ECS by the real-time iontophoretic method demonstrated that ECS volume was selectively reduced in the stratum pyramidale by ?40% in Has3?/? mice. Finally, osmotic manipulation experiments in brain slices from Has3?/? and wild-type mice provided evidence for a causal link between ECS volume and epileptiform activity. Our results provide the first direct evidence for the physiological role of HA in the regulation of ECS volume, and suggest that HA-based preservation of ECS volume may offer a novel avenue for development of antiepileptogenic treatments. PMID:24790187
Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain
Zhang, Xiaowei; Bearer, Elaine L.; Boulat, Benoit; Hall, F. Scott; Uhl, George R.; Jacobs, Russell E.
The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn2+ into the prefrontal cortex indicated that DAT KO mice have a truncated Mn2+ distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn2+ transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here. PMID:20634895
Predicting intrinsic brain activity.
Craddock, R Cameron; Milham, Michael P; LaConte, Stephen M
Multivariate supervised learning methods exhibit a remarkable ability to decode externally driven sensory, behavioral, and cognitive states from functional neuroimaging data. Although they are typically applied to task-based analyses, supervised learning methods are equally applicable to intrinsic effective and functional connectivity analyses. The obtained models of connectivity incorporate the multivariate interactions between all brain regions simultaneously, which will result in a more accurate representation of the connectome than the ones available with standard bivariate methods. Additionally the models can be applied to decode or predict the time series of intrinsic brain activity of a region from an independent dataset. The obtained prediction accuracy provides a measure of the integration between a brain region and other regions in its network, as well as a method for evaluating acquisition and preprocessing pipelines for resting state fMRI data. This article describes a method for learning multivariate models of connectivity. The method is applied in the non-parametric prediction accuracy, influence, and reproducibility-resampling (NPAIRS) framework, to study the regional variation of prediction accuracy and reproducibility (Strother et al., 2002). The resulting spatial distribution of these metrics is consistent with the functional hierarchy proposed by Mesulam (1998). Additionally we illustrate the utility of the multivariate regression connectivity modeling method for optimizing experimental parameters and assessing the quality of functional neuroimaging data. PMID:23707580
Short-term exposure to nickel alters the adult rat brain antioxidant status and the activities of crucial membrane-bound enzymes: neuroprotection by L-cysteine.
Liapi, Charis; Zarros, Apostolos; Theocharis, Stamatios; Voumvourakis, Konstantinos; Anifantaki, Foteini; Gkrouzman, Elena; Mellios, Zois; Skandali, Nikolina; Al-Humadi, Hussam; Tsakiris, Stylianos
Nickel (Ni) is an environmental pollutant towards which human exposure can be both occupational (mainly through inhalation) and dietary (through water and food chain-induced bioaccumulation). The aim of this study was to investigate the effects of short-term Ni-administration (as NiCl(2), 13 mg/kg) on the adult rat whole brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na(+),K(+)-ATPase, and Mg(2+)-ATPase; in addition, the potential effect of the co-administration of the antioxidant L-cysteine (Cys, 7 mg/kg) on the above parameters was studied. Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (Ni), C (Cys), and D (Ni and Cys). All rats were treated once daily with intraperitoneal injections of the tested compounds, for 1-week. Rats were sacrificed by decapitation and the above-mentioned parameters were measured spectrophotometrically. Rats treated with Ni exhibited a significant reduction in brain TAS (-47%, p?0.001, BvsA) that was efficiently limited by the co-administration of Cys (-4%, p?>?0.05, DvsA; +83%, p?0.001, DvsB), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both Ni (+30%, p?0.001, BvsA) and Cys (+62%, p?0.001, CvsA), while it tended to adjust to control levels by the co-administration of Ni and Cys (+13%, p?0.001, DvsA; -13%, p?0.001, DvsB). The activity of rat brain Na(+),K(+)-ATPase was significantly decreased by Ni-administration (-49%, p?0.001, BvsA), while Cys supplementation could not reverse this decrease (-44%, p?0.001, DvsA). The activity of Mg(2+)-ATPase was not affected by Ni-administration (-3%, p?>?0.05, BvsA), but was significantly reduced when combined with Cys administration (-17%, p?0.001, DvsA). The above findings suggest that Ni short-term in vivo administration causes a statistically significant decrease in the rat brain TAS and an increase in AChE activity. Both effects can be, partially or totally, reversed to control levels by Cys co-administration; Cys could thus be considered (for future applications) as a potential neuroprotective agent against chronic exposure to Ni. The activity of Na(+),K(+)-ATPase that was inhibited by Ni, could not be reversed by Cys co-administration. The matter requires further investigation in order to fully elucidate the spectrum of the neurotoxic effects of Ni. PMID:21360057
Altered Metabolism in Frontal Brain Circuits in Cluster Headache
T Sprenger; KV Ruether; H Boecker; M Valet; A Berthele; V Pfaffenrath; A Wöller; TR Tölle
Neuroimaging studies have explored cerebral activation patterns in patients with cluster headache (CH) during attacks and have revealed activation of multiple brain areas known to belong to the general pain-processing network. However, it is still unclear which changes in brain metabolism are inherent to the shift from the 'in bout' to the 'out of bout' period. We measured cerebral glucose
Lesions of area postrema and subfornical organ alter exendin-4-induced brain activation without preventing the hypophagic effect of the GLP-1 receptor agonist.
Baraboi, Elena-Dana; Smith, Pauline; Ferguson, Alastair V; Richard, Denis
The mechanism and route whereby glucagon-like peptide 1 (GLP-1) receptor agonists, such as GLP-1 and exendin-4 (Ex-4), access the central nervous system (CNS) to exert their metabolic effects have yet to be clarified. The primary objective of the present study was to investigate the potential role of two circumventricular organs (CVOs), the area postrema (AP) and the subfornical organ (SFO), in mediating the metabolic and CNS-stimulating effects of Ex-4. We demonstrated that electrolytic ablation of the AP, SFO, or AP + SFO does not acutely prevent the anorectic effects of Ex-4. AP + SFO lesion chronically decreased food intake and body weight and also modulated the effect of Ex-4 on the neuronal activation of brain structures involved in the hypothalamic-pituitary-adrenal axis and glucose metabolism. The results of the study also showed that CVO lesions blunted Ex-4-induced expression of c-fos mRNA (a widely used neuronal activity marker) in 1) limbic structures (bed nucleus of the stria terminalis and central amygdala), 2) hypothalamus (paraventricular hypothalamic nucleus, supraoptic nucleus, and arcuate nucleus), and 3) hindbrain (lateral and lateral-external parabrachial nucleus, medial nucleus of the solitary tract, and ventrolateral medulla). In conclusion, although the present results do not support a role for the CVOs in the anorectic effect induced by a single injection of Ex-4, they suggest that the CVOs play important roles in mediating the actions of Ex-4 in the activation of CNS structures involved in homeostatic control. PMID:20106992
Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice.
C, Jadiswami; H M, Megha; Dhadde, Shivsharan B; Durg, Sharanbasappa; Potadar, Pandharinath P; B S, Thippeswamy; V P, Veerapur
3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington's disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20?mg/kg, i.p.) 30?min before 3-NP challenge (15?mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions. PMID:25191831
Brain Gym. Simple Activities for Whole Brain Learning.
ERIC Educational Resources Information Center
Dennison, Paul E.; Dennison, Gail E.
This booklet contains simple movements and activities that are used with students in Educational Kinesiology to enhance their experience of whole brain learning. Whole brain learning through movement repatterning and Brain Gym activities enable students to access those parts of the brain previously unavailable to them. These movements of body and…
Brain alterations within the first 100 days of HIV infection
Ragin, Ann B; Wu, Ying; Gao, Yi; Keating, Sheila; Du, Hongyan; Sammet, Christina; Kettering, Casey S; Epstein, Leon G
Objective Brain involvement is a serious complication of HIV infection. The earliest changes in the brain, which represents an anatomic site for viral persistence, are largely unknown. Methods This investigation used quantitative Magnetic Resonance methodologies, including high resolution and diffusion tensor (DTI) imaging, to evaluate the brain in 15 HIV and 20 seronegative subjects. All HIV subjects were antibody nonreactive with assay-estimated infection duration of less than 100 days. Results Brain volumetric analysis revealed reduced parenchyma with enlargement of the third ventricle and brainstem. DTI quantified loss of white matter integrity in the corpus callosum and diffusion alterations in caudate. Cognitive differences were indicated in psychomotor speed and visual recall. There were no differences between antiretroviral-initiated and naďve HIV subgroups. Interpretation These findings, quantified within 100 days of infection, shed light on the earliest brain changes in HIV infection. Onset of neural injury may date to initial viral invasion and the transient early period of unchecked viremia and marked immunosuppression of the seroconversion period. PMID:25642430
Introducing graph theory to track for neuroplastic alterations in the resting human brain: A transcranial direct current stimulation study
Rafael Polanía; Walter Paulus; Andrea Antal; Michael A. Nitsche
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability and activity in a polarity-dependent way. Stimulation for a few minutes has been shown to induce plastic alterations of cortical excitability and to improve cognitive performance. These effects might be related to stimulation-induced alterations of functional cortical network connectivity. We aimed to investigate the impact
Brain structural alterations associated with young women with subthreshold depression
Li, Haijiang; Wei, Dongtao; Sun, Jiangzhou; Chen, Qunlin; Zhang, Qinglin; Qiu, Jiang
Neuroanatomical abnormalities in patients with major depression disorder (MDD) have been attracted great research attention. However, the structural alterations associated with subthreshold depression (StD) remain unclear and, therefore, require further investigation. In this study, 42 young women with StD, and 30 matched non-depressed controls (NCs) were identified based on two-time Beck Depression Inventory scores. Whole-brain voxel-based morphometry (VBM) and region of interest method were used to investigate altered gray matter volume (GMV) and white matter volume (WMV) among a non-clinical sample of young women with StD. VBM results indicated that young women with StD showed significantly decreased GMV in the right inferior parietal lobule than NCs; increased GMV in the amygdala, posterior cingulate cortex, and precuneus; and increased WMV in the posterior cingulate cortex and precuneus. Together, structural alterations in specific brain regions, which are known to be involved in the fronto-limbic circuits implicated in depression may precede the occurrence of depressive episodes and influence the development of MDD. PMID:25982857
Brain structural alterations associated with young women with subthreshold depression.
Li, Haijiang; Wei, Dongtao; Sun, Jiangzhou; Chen, Qunlin; Zhang, Qinglin; Qiu, Jiang
Neuroanatomical abnormalities in patients with major depression disorder (MDD) have been attracted great research attention. However, the structural alterations associated with subthreshold depression (StD) remain unclear and, therefore, require further investigation. In this study, 42 young women with StD, and 30 matched non-depressed controls (NCs) were identified based on two-time Beck Depression Inventory scores. Whole-brain voxel-based morphometry (VBM) and region of interest method were used to investigate altered gray matter volume (GMV) and white matter volume (WMV) among a non-clinical sample of young women with StD. VBM results indicated that young women with StD showed significantly decreased GMV in the right inferior parietal lobule than NCs; increased GMV in the amygdala, posterior cingulate cortex, and precuneus; and increased WMV in the posterior cingulate cortex and precuneus. Together, structural alterations in specific brain regions, which are known to be involved in the fronto-limbic circuits implicated in depression may precede the occurrence of depressive episodes and influence the development of MDD. PMID:25982857
Fueling and imaging brain activation
Dienel, Gerald A
Metabolic signals are used for imaging and spectroscopic studies of brain function and disease and to elucidate the cellular basis of neuroenergetics. The major fuel for activated neurons and the models for neuron–astrocyte interactions have been controversial because discordant results are obtained in different experimental systems, some of which do not correspond to adult brain. In rats, the infrastructure to support the high energetic demands of adult brain is acquired during postnatal development and matures after weaning. The brain's capacity to supply and metabolize glucose and oxygen exceeds demand over a wide range of rates, and the hyperaemic response to functional activation is rapid. Oxidative metabolism provides most ATP, but glycolysis is frequently preferentially up-regulated during activation. Underestimation of glucose utilization rates with labelled glucose arises from increased lactate production, lactate diffusion via transporters and astrocytic gap junctions, and lactate release to blood and perivascular drainage. Increased pentose shunt pathway flux also causes label loss from C1 of glucose. Glucose analogues are used to assay cellular activities, but interpretation of results is uncertain due to insufficient characterization of transport and phosphorylation kinetics. Brain activation in subjects with low blood-lactate levels causes a brain-to-blood lactate gradient, with rapid lactate release. In contrast, lactate flooding of brain during physical activity or infusion provides an opportunistic, supplemental fuel. Available evidence indicates that lactate shuttling coupled to its local oxidation during activation is a small fraction of glucose oxidation. Developmental, experimental, and physiological context is critical for interpretation of metabolic studies in terms of theoretical models. PMID:22612861
Does acute caffeine ingestion alter brain metabolism in young adults?
Xu, Feng; Liu, Peiying; Pekar, James J; Lu, Hanzhang
Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain's response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine's effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657
Cortisol's effects on hippocampal activation in depressed patients are related to alterations in memory formation
Wisconsin at Madison, University of
Cortisol's effects on hippocampal activation in depressed patients are related to alterations Keywords: Hippocampus Cortisol Memory Depression fMRI Emotion a b s t r a c t Many investigators have hypothesized that brain response to cortisol is altered in depression. However, neural activation in response
Sodium tungstate induced neurological alterations in rat brain regions and their response to antioxidants.
Sachdeva, Sherry; Pant, Satish C; Kushwaha, Pramod; Bhargava, Rakesh; Flora, Swaran J S
Tungsten, recognized recently as an environmental contaminant, is being used in arms and ammunitions as substitute to depleted uranium. We studied the effects of sodium tungstate on oxidative stress, few selected neurological variables like acetylcholinesterase, biogenic amines in rat brain regions (cerebral cortex, hippocampus and cerebellum) and their prevention following co-administration of N-acetylcysteine (NAC), naringenin and quercetin. Animals were sub-chronically exposed to sodium tungstate (100?ppm in drinking water) and orally co-supplemented with different antioxidants (0.30?mM) for three months. Sodium tungstate significantly decreased the activity of acetylcholinesterase, dopamine, nor-epinephrine and 5-hydroxytryptamine levels while it increased monoamine oxidase activity in different brain regions. Tungstate exposure produced a significant increase in biochemical variables indicative of oxidative stress while, neurological alterations were more pronounced in the cerebral cortex compared to other regions. Co-administration of NAC and flavonoids with sodium tungstate significantly restored glutathione, prevented changes in the brain biogenic amines, reactive oxygen species (ROS) and TBARS levels in the different brain regions. The protection was more prominent in the animals co-administered with NAC. We can thus conclude that sodium tungstate induced brain oxidative stress and the alterations in some neurological variables can effectively be reduced by co-supplementation of NAC. PMID:25983264
Alterations of excitatory amino acid receptors in the brain of managese-treated mice
Georgina Cano; Heberto Suárez-Roca; Ernesto Bonilla
An excessive activation of excitatory amino acid (EAA) receptors has been associated with oxidative stress, which is considered\\u000a the primary cause of manganese (Mn) poisoning neurotoxicity. Therefore, the EAA receptor distribution was analyzed by autoradiographic\\u000a methods in several brain regions during Mn intoxication. We found that chronic treatment of mice with MnCl2 during 8 wk significantly alters thel-[3H]glutamate (l-[3H]Glu) binding
The Epoch Times | Cocaine Alters Brain Cells, Impairs Impulse Control < Back to previous page
Goldstein, Rita
The Epoch Times | Cocaine Alters Brain Cells, Impairs Impulse Control > Health Cocaine Alters Brain Cells, Impairs Impulse Control Reuters Oct 18, 2006 NEW YORK--A number in Atlanta, show that cocaine use negatively affects the functioning of neurons (cells located in the brain
Decoding Patterns of Human Brain Activity
Tong, Frank
Decoding Patterns of Human Brain Activity Frank Tong and Michael S. Pratte Psychology Department be decoded from noninvasive measures of human brain activity. Analyses of brain activ- ity patterns can into a neuroimaging lab and asked to lie back comfortably on a padded bed ta- ble, which is slowly glided into a brain
Alterations in Brain and Immune Function Produced by Mindfulness RICHARD J. DAVIDSON, PHD, JON KABAT-ZINN, PHD, JESSICA SCHUMACHER, MS, MELISSA ROSENKRANZ, BA,
Hunter, David
Alterations in Brain and Immune Function Produced by Mindfulness Meditation RICHARD J. DAVIDSON performed a randomized, controlled study on the effects on brain and immune function of a well with healthy employees. Methods: We measured brain electrical activity before and immediately after, and then 4
Models of brain injury and alterations in synaptic plasticity.
Albensi, B C
Animal models are crucial for understanding human pathophysiological processes and for understanding how connections are injured, lost, or even regenerated and/or repaired. When animal models are used in conjunction with theoretical computational models, an ideal combination is achieved that potentially yields insight and encourages the formation of new theories concerning connectionism, cognitive functioning, and synaptic mechanisms. Mechanisms regulating glutamate receptor activation and intracellular calcium levels are important for normal synaptic transmission. These mechanisms (and others) are also critical during and after brain injury when the potential exists for these mechanisms to function pathologically. Interestingly enough, the regulation of glutamate receptor activation and intracellular calcium levels is also involved in normal processes of neuronal and synaptic plasticity. In addition, studies have shown that neurotrophins and cytokines, which are released after brain injury, can be neuroprotective and may also be important in synaptic plasticity. Furthermore, synaptic plasticity is a phenomenon thought by many to be necessary for memory encoding. If this is the case, then research described in this review has significant scientific merit concerning plasticity and memory and clinical benefit for understanding pathophysiologic processes associated with brain injury and memory impairment. This paper reviews the application of experimental animal models of brain injury for simulating conditions of stroke, trauma, and epilepsy (and/or seizure generation) and the associated cellular mechanisms of brain injury. The paper also briefly addresses the advantage of using computational models in combination with experimental models for hypothesis building and for aiding in the interpretation of empirical data. Finally, it reviews studies concerning brain injury and synaptic plasticity. PMID:11494362
Decoding Patterns of Human Brain Activity
Frank Tong; Michael S. Pratte
Considerable information about mental states can be decoded from noninvasive measures of human brain activity. Analyses of brain activity patterns can reveal what a person is seeing, perceiving, attending to, or remembering. Moreover, multidimensional models can be used to investigate how the brain encodes complex visual scenes or abstract semantic information. Such feats of "brain reading" or "mind reading," though
Decoding Patterns of Human Brain Activity
Frank Tong; Michael S. Pratte
Considerable information about mental states can be decoded from noninvasive measures of human brain activity. Analyses of brain activity patterns can reveal what a person is seeing, perceiving, attending to, or remembering. Moreover, multidimensional models can be used to investigate how the brain encodes complex visual scenes or abstract semantic information. Such feats of "brain reading" or "mind reading," though
Prion disease induced alterations in gene expression in spleen and brain prior to clinical symptoms
Kim, Hyeon O; Snyder, Greg P; Blazey, Tyler M; Race, Richard E; Chesebro, Bruce; Skinner, Pamela J
Prion diseases are fatal neurodegenerative disorders that affect animals and humans. There is a need to gain understanding of prion disease pathogenesis and to develop diagnostic assays to detect prion diseases prior to the onset of clinical symptoms. The goal of this study was to identify genes that show altered expression early in the disease process in the spleen and brain of prion disease-infected mice. Using Affymetrix microarrays, we identified 67 genes that showed increased expression in the brains of prion disease-infected mice prior to the onset of clinical symptoms. These genes function in many cellular processes including immunity, the endosome/lysosome system, hormone activity, and the cytoskeleton. We confirmed a subset of these gene expression alterations using other methods and determined the time course in which these changes occur. We also identified 14 genes showing altered expression prior to the onset of clinical symptoms in spleens of prion disease infected mice. Interestingly, four genes, Atp1b1, Gh, Anp32a, and Grn, were altered at the very early time of 46 days post-infection. These gene expression alterations provide insights into the molecular mechanisms underlying prion disease pathogenesis and may serve as surrogate markers for the early detection and diagnosis of prion disease. PMID:21918605
AQP4 gene deletion in mice does not alter blood–brain barrier integrity or brain morphology
S. Saadoun; M. J. Tait; A. Reza; D. Ceri Davies; B. A. Bell; A. S. Verkman; M. C. Papadopoulos
The glial cell water channel aquaporin-4 (AQP4) plays an important role in brain edema, astrocyte migration, and neuronal excitability. Zhou et al. [Zhou J, Kong H, Hua X, Xiao M, Ding J, Hu G (2008) Altered blood–brain barrier integrity in adult aquaporin-4 knockout mice. Neuroreport 19:1–5] recently reported that AQP4 deletion significantly altered blood–brain barrier integrity and glial fibrillary acidic
Irradiation induces regionally specific alterations in pro-inflammatory environments in rat brain
Lee, Won Hee; Sonntag, William E.; Mitschelen, Matthew; Yan, Han; Lee, Yong Woo
Purpose Pro-inflammatory environments in the brain have been implicated in the onset and progression of neurological disorders. In the present study, we investigate the hypothesis that brain irradiation induces regionally specific alterations in cytokine gene and protein expression. Materials and methods Four month old F344 × BN rats received either whole brain irradiation with a single dose of 10 Gy ?-rays or sham-irradiation, and were maintained for 4, 8, and 24 h following irradiation. The mRNA and protein expression levels of pro-inflammatory mediators were analysed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. To elucidate the molecular mechanisms of irradiation-induced brain inflammation, effects of irradiation on the DNA-binding activity of pro-inflammatory transcription factors were also examined. Results A significant and marked up-regulation of mRNA and protein expression of pro-inflammatory mediators, including tumour necrosis factor-? (TNF-?), interleukin-1? (IL-1?), and monocyte chemoattractant protein-1 (MCP-1), was observed in hippocampal and cortical regions isolated from irradiated brain. Cytokine expression was regionally specific since TNF-? levels were significantly elevated in cortex compared to hippocampus (57% greater) and IL-1? levels were elevated in hippocampus compared to cortical samples (126% greater). Increases in cytokine levels also were observed after irradiation of mouse BV-2 microglial cells. A series of electrophoretic mobility shift assays (EMSA) demonstrated that irradiation significantly increased activation of activator protein-1 (AP-1), nuclear factor-?B (NF-?B), and cAMP response element-binding protein (CREB). Conclusion The present study demonstrated that whole brain irradiation induces regionally specific pro-inflammatory environments through activation of AP-1, NF-?B, and CREB and overexpression of TNF-?, IL-1?, and MCP-1 in rat brain and may contribute to unique pathways for the radiation-induced impairments in tissue function. PMID:20148699
Reduced brain functional reserve and altered functional connectivity in patients with multiple sclerosis.
Cader, Sarah; Cifelli, Alberto; Abu-Omar, Yasir; Palace, Jacqueline; Matthews, Paul M
Cognitive dysfunction (affecting particularly attention and working memory) occurs early in patients with multiple sclerosis. Previous studies have focused on identifying potentially adaptive functional reorganization through recruitment of new brain regions that could limit expression of these deficits. However, lesion studies remind us that functional specializations in the brain make certain brain regions necessary for a given task. We therefore have asked whether altered functional interactions between regions normally recruited provide an alternative adaptive mechanism with multiple sclerosis pathology. We used a version of the n-back task to probe working memory in patients with early multiple sclerosis. We applied a functional connectivity analysis to test whether relationships between relative activations in different brain regions change in potentially adaptive ways with multiple sclerosis. We studied 21 patients with relapsing-remitting multiple sclerosis and 16 age- and sex-matched healthy controls with 3T functional MRI. The two groups performed equally well on the task. Task-related activations were found in similar regions for patients and controls. However, patients showed relatively reduced activation in the superior frontal and anterior cingulate gyri (P > 0.01). Patients also showed a variable, but generally substantially smaller increase in activation than healthy controls with greater task complexity, depending on the specific brain region assessed (P < 0.001). Functional connectivity analysis defined further differences not apparent from the univariate contrast of the task-associated activation patterns. Control subjects showed significantly greater correlations between right dorsolateral prefrontal and superior frontal/anterior cingulate activations (P < 0.05). Patients showed correlations between activations in the right and left prefrontal cortices, although this relationship was not significant in healthy controls (P < 0.05). We interpret these results as showing that, while cognitive processing in the task appears to be performed using similar brain regions in patients and controls, the patients have reduced functional reserve for cognition relevant to memory. Functional connectivity analysis suggests that altered inter-hemispheric interactions between dorsal and lateral prefrontal regions may provide an adaptive mechanism that could limit clinical expression of the disease distinct from recruitment of novel processing regions. Together, these results suggest that therapeutic enhancement of the coherence of interactions between brain regions normally recruited (functional enhancement), as well as recruitment of alternative areas or use of complementary cognitive strategies (both forms of adaptive functional change), may limit expression of cognitive impairments in multiple sclerosis. PMID:16251214
Insulin resistance in brain alters dopamine turnover and causes behavioral disorders.
Kleinridders, Andre; Cai, Weikang; Cappellucci, Laura; Ghazarian, Armen; Collins, William R; Vienberg, Sara G; Pothos, Emmanuel N; Kahn, C Ronald
Diabetes and insulin resistance are associated with altered brain imaging, depression, and increased rates of age-related cognitive impairment. Here we demonstrate that mice with a brain-specific knockout of the insulin receptor (NIRKO mice) exhibit brain mitochondrial dysfunction with reduced mitochondrial oxidative activity, increased levels of reactive oxygen species, and increased levels of lipid and protein oxidation in the striatum and nucleus accumbens. NIRKO mice also exhibit increased levels of monoamine oxidase A and B (MAO A and B) leading to increased dopamine turnover in these areas. Studies in cultured neurons and glia cells indicate that these changes in MAO A and B are a direct consequence of loss of insulin signaling. As a result, NIRKO mice develop age-related anxiety and depressive-like behaviors that can be reversed by treatment with MAO inhibitors, as well as the tricyclic antidepressant imipramine, which inhibits MAO activity and reduces oxidative stress. Thus, insulin resistance in brain induces mitochondrial and dopaminergic dysfunction leading to anxiety and depressive-like behaviors, demonstrating a potential molecular link between central insulin resistance and behavioral disorders. PMID:25733901
High-Resolution Genome-Wide Mapping of Genetic Alterations in Human Glial Brain Tumors
Ford, James
High-Resolution Genome-Wide Mapping of Genetic Alterations in Human Glial Brain Tumors Markus and showed that gliomas can be clustered into distinct genetic subgroups. A subset of detected alterations are key genetic events in gliomagenesis. Recurrent genomic regions of alteration in copy number, including
Focused ultrasound modulates region-specific brain activity
Yoo, Seung-Schik; Bystritsky, Alexander; Lee, Jong-Hwan; Zhang, Yongzhi; Fischer, Krisztina; Min, Byoung-Kyong; McDannold, Nathan J.; Pascual-Leone, Alvaro; Jolesz, Ferenc A.
We demonstrated the in vivo feasibility of using focused ultrasound (FUS) to transiently modulate (through either stimulation or suppression) the function of regional brain tissue in rabbits. FUS was delivered in a train of pulses at low acoustic energy, far below the cavitation threshold, to the animal's somatomotor and visual areas, as guided by anatomical and functional information from magnetic resonance imaging (MRI). The temporary alterations in the brain function affected by the sonication were characterized by both electrophysiological recordings and functional brain mapping achieved through the use of functional MRI (fMRI). The modulatory effects were bimodal, whereby the brain activity could either be stimulated or selectively suppressed. Histological analysis of the excised brain tissue after the sonication demonstrated that the FUS did not elicit any tissue damages. Unlike transcranial magnetic stimulation, FUS can be applied to deep structures in the brain with greater spatial precision. Transient modulation of brain function using image-guided and anatomically-targeted FUS would enable the investigation of functional connectivity between brain regions and will eventually lead to a better understanding of localized brain functions. It is anticipated that the use of this technology will have an impact on brain research and may offer novel therapeutic interventions in various neurological conditions and psychiatric disorders. PMID:21354315
Alcohol exposure alters the expression pattern of neural cell adhesion molecules during brain development.
Mińana, R; Climent, E; Barettino, D; Segui, J M; Renau-Piqueras, J; Guerri, C
Neural cell adhesion molecules (NCAMs) play critical roles during development of the nervous system. The aim of this study is to investigate the possible effect of ethanol exposure on the pattern of expression and sialylation of NCAM isoforms during postnatal rat brain development because alterations in NCAM content and distribution have been associated with defects in cell migration, synapse formation, and memory consolidation, and deficits in these processes have been observed after in utero alcohol exposure. The expression of NCAM isoforms in the developing cerebral cortex of pups from control and alcohol-fed mothers was assessed by western blotting, ribonuclease protection assay, and immunocytochemistry. The highly sialylated form of NCAM [polysialic acid (PSA)-NCAM] is mainly expressed during the neonatal period and then is down-regulated in parallel with the appearance of NCAM 180 and NCAM 140. Ethanol exposure increases PSA-NCAM levels during the neonatal period, delays the loss of PSA-NCAM, decreases the amount of NCAM 180 and NCAM 140 isoforms, and reduces sialyltransferase activity during postnatal brain development. Neuraminidase treatment of ethanol-exposed neonatal brains leads to more intense band degradation products, suggesting a higher content of NCAM polypeptides carrying PSA in these samples. However, NCAM mRNA levels are not changed by ethanol. Immunocytochemical analysis demonstrates that ethanol triggers an increase in PSA-NCAM immunolabeling in the cytoplasm of astroglial cells, accompanied by a decrease in immunogold particles over the plasma membrane. These findings indicate that ethanol exposure during brain development alters the pattern of NCAM expression and suggest that modification of NCAM could affect neuronal-glial interactions that might contribute to the brain defects observed after in utero alcohol exposure. PMID:10936176
A default mode of brain function in altered states of consciousness.
Guldenmund, P; Vanhaudenhuyse, A; Boly, M; Laureys, S; Soddu, A
Using modern brain imaging techniques, new discoveries are being made concerning the spontaneous activity of the brain when it is devoid of attention-demanding tasks. Spatially separated patches of neuronal assemblies have been found to show synchronized oscillatory activity behavior and are said to be functionally connected. One of the most robust of these is the default mode network, which is associated with intrinsic processes like mind wandering and self-projection. Furthermore, activity in this network is anticorrelated with activity in a network that is linked to attention to external stimuli. The integrity of both networks is disturbed in altered states of consciousness, like sleep, general anesthesia and hypnosis. In coma and related disorders of consciousness, encompassing the vegetative state (unresponsive wakefulness syndrome) and minimally conscious state, default mode network integrity correlates with the level of remaining consciousness, offering the possibility of using this information for diagnostic and prognostic purposes. Functional brain imaging is currently being validated as a valuable addition to the standardized behavioral assessments that are already in use. PMID:23165872
Research Article Human Brain Activity Time-
Zacks, Jeffrey M.
Research Article Human Brain Activity Time- Locked to Narrative Event Boundaries Nicole K. Speer into a series of events in order to understand and remember the text. In this study, subjects read brief narratives describing every- day activities while brain activity was recorded with functional magnetic
Developmental Hypothyroidism Alters Brain-Derived Neurotrophic Factor (BDNF) Expression in Adulthood.
Severe developmental thyroid hormone (TH) insufficiency results in alterations in brain structure/function and lasting behavioral impairments. Environmental toxicants reduce circulating levels of TH, but the disruption is modest and the doseresponse relationships of TH and neuro...
Myelin alters the inflammatory phenotype of macrophages by activating PPARs
Background Foamy macrophages, containing myelin degradation products, are abundantly found in active multiple sclerosis (MS) lesions. Recent studies have described an altered phenotype of macrophages after myelin internalization. However, mechanisms by which myelin affects the phenotype of macrophages and how this phenotype influences lesion progression remain unclear. Results We demonstrate that myelin as well as phosphatidylserine (PS), a phospholipid found in myelin, reduce nitric oxide production by macrophages through activation of peroxisome proliferator-activated receptor ?/? (PPAR?/?). Furthermore, uptake of PS by macrophages, after intravenous injection of PS-containing liposomes (PSLs), suppresses the production of inflammatory mediators and ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The protective effect of PSLs in EAE animals is associated with a reduced immune cell infiltration into the central nervous system and decreased splenic cognate antigen specific proliferation. Interestingly, PPAR?/? is activated in foamy macrophages in active MS lesions, indicating that myelin also activates PPAR?/? in macrophages in the human brain. Conclusion Our data show that myelin modulates the phenotype of macrophages by PPAR activation, which may subsequently dampen MS lesion progression. Moreover, our results suggest that myelin-derived PS mediates PPAR?/? activation in macrophages after myelin uptake. The immunoregulatory impact of naturally-occurring myelin lipids may hold promise for future MS therapeutics. PMID:24252308
r Human Brain Mapping 00:000000 (2012) r Key Functional Circuitry Altered in Schizophrenia
Feng, Jianfeng
r Human Brain Mapping 00:000000 (2012) r Key Functional Circuitry Altered in Schizophrenia functional and structural changes in the brain in schizophrenia are of most importance, although the main schizophrenia patients, and func- tional connectivity changes were analyzed using resting-state fMRI data from
Alteration of BloodBrain Barrier Integrity by Retroviral Philippe V. Afonso1
Paris-Sud XI, Université de
Alteration of BloodBrain Barrier Integrity by Retroviral Infection Philippe V. Afonso1 , Simona Cellulaire, CNRS 8104/INSERM 567/Paris V, Institut Cochin, Paris, France Abstract The bloodbrain barrier and astrocytes. Although astrocytes have been shown to be infected by HTLV-1, until now, little was known about
Probing Brain Reward System Function in Major Depressive Disorder: Altered Response to Dextroamphetamine
Lescia K. Tremblay; Claudio A. Naranjo; Laura Cardenas; Nathan Herrmann; Usoa E. Busto
Background: The state of the brain reward system in major depressive disorder was assessed with dextroam- phetamine, which probes the release of dopamine within the mesocorticolimbic system, a major component of the brain reward system, and produces measurable behav- ioral changes, including rewarding effects (eg, eupho- ria). We hypothesized that depressed individuals would exhibit an altered response to dextroamphetamine due
Sustained deep-tissue pain alters functional brain connectivity Jieun Kim a,
Napadow, Vitaly
Sustained deep-tissue pain alters functional brain connectivity Jieun Kim a, , Marco L. Loggia a connec- tivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific connectivity a b s t r a c t Recent functional brain connectivity studies have contributed to our understanding
Behavioral/Systems/Cognitive Deep Brain Stimulation of the Subthalamic Nucleus Alters
Aron, Adam
Behavioral/Systems/Cognitive Deep Brain Stimulation of the Subthalamic Nucleus Alters the CorticalMRI, and transcranial magnetic stimulation studies, points to a specific brain system for stopping, including the right and reported an enhancement in the beta-band for NoGo compared to Go trials (Ku¨hn et al., 2004). These studies
Neural Activity and the Development of Brain
Sur, Mriganka
Neural Activity and the Development of Brain Circuits Carsten D Hohnke, Massachusetts Institute, Massachusetts, USA The development of highly interconnected circuits in the brain relies on patterns of neural into precise circuits. The presence of neural activity is particularly important during well-defined critical
Perinatal Risk Factors Altering Regional Brain Structure in the Preterm Infant
ERIC Educational Resources Information Center
Thompson, Deanne K.; Warfield, Simon K.; Carlin, John B.; Pavlovic, Masa; Wang, Hong X.; Bear, Merilyn; Kean, Michael J.; Doyle, Lex W.; Egan, Gary F.; Inder, Terrie E.
Neuroanatomical structure appears to be altered in preterm infants, but there has been little insight into the major perinatal risk factors associated with regional cerebral structural alterations. MR images were taken to quantitatively compare regional brain tissue volumes between term and preterm infants and to investigate associations between…
Chronic Alcohol Drinking Alters Neuronal Dendritic Spines in the Brain Reward Center Nucleus Accumbens
New York at Stoney Brook, State University of
Zhou et al 1 Chronic Alcohol Drinking Alters Neuronal Dendritic Spines in the Brain Reward Center Running Title: Chronic Alcohol Alters Neurodendritic Structure 9 figures and 1 table Send all of Neuroscience For Peer Review Only #12;Zhou et al 2 ABSTRACT Alcohol is known to affect glutamate transmission
Altered resting brain connectivity in persistent cancer related fatigue
Hampson, Johnson P.; Zick, Suzanna M.; Khabir, Tohfa; Wright, Benjamin D.; Harris, Richard E.
There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF) disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued) who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI). Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected). This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52) and poor sleep quality (P = 0.04, r = 0.52) in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected). Mental fatigue scores were associated with greater default mode network (DMN) connectivity to the superior frontal gyrus (P = 0.05 FDR corrected) among fatigued subjects (r = 0.82) and less connectivity in the non-fatigued group (r = ?0.88). These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent fatigue. As the DMN is a network involved in self-referential thinking we speculate that enhanced connectivity between the DMN and the frontal gyrus may be related to mental fatigue and poor sleep quality. In contrast, enhanced connectivity between the DMN and regions in the subgenual cingulate and brainstem may serve a protective function in the non-fatigued group.
The restless brain: how intrinsic activity organizes brain function
Raichle, Marcus E.
Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease. PMID:25823869
Alterations in Human EEG Activity Caused by Extremely Low Frequency Electromagnetic Fields
D. Cvetkovic; E. Jovanov; I. Cosic
This study has investigated whether extremely low frequency (ELF) electromagnetic fields (EMFs) can alter human brain activity. Linearly polarised magnetic flux density of 20 muT (rms) was generated using a standard double Helmholtz coils and applied to the human head over a sequence of 1 minute stimulations followed by one minute without stimulation in the following order of frequencies 50,
Enzymatic activities in brains of diabetic rats treated with vanadyl sulphate and sodium tungstate.
Lemberg, A; Fernández, M A; Ouvińa, G; Rodríguez, R R; Peredo, H A; Susemihl, C; Villarreal, I; Filinger, E J
The hypothesis of the present study was that diabetes mellitus might affect brain metabolism. Streptozotocin (STZ)-induced diabetic rats, treated with vanadyl sulphate (V) and sodium tungstate (T) were employed to observe the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) activities in brain homogenates. Significant increases in AST, ALT and CK activities were found in diabetic brain homogenates against controls, suggesting increments of transamination in brain and/or increases in cell membrane permeability to these enzymes. The increase in brain CK possibly expresses alterations in energy production. The decrease in CK activity caused by V and T treatment in diabetic rats suggests that both agents tend to normalize energy consumption. It is also possible that V and T-induced hypoglycemic effects cause metabolic alterations in brain. PMID:18038759
Systemic Neurochemical Alterations in Schizophrenic Brain: Glutamate Metabolism in Focus
Gulnur Sh. Burbaeva; Irina S. Boksha; Elena B. Tereshkina; Olga K. Savushkina; Lubov' I. Starodubtseva; Marina S. Turishcheva; Elizabeta Mukaetova-Ladinska
We have used a systemic approach to establish a relationship between enzyme measures of glial glutamate and energy metabolism\\u000a (glutamine synthetase and glutamine synthetase-like protein, glutamate dehydrogenase isoenzymes, brain isoform creatine phosphokinase)\\u000a and two major glial proteins (glial fibrillary acidic protein and myelin basic protein) in autopsied brain samples taken from\\u000a patients with schizophrenia (SCH) and mentally healthy subjects (23
Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer.
Kesler, Shelli R; Watson, Christa L; Blayney, Douglas W
Breast cancer and its treatments are associated with mild cognitive impairment and brain changes that could indicate an altered or accelerated brain aging process. We applied diffusion tensor imaging and graph theory to measure white matter organization and connectivity in 34 breast cancer survivors compared with 36 matched healthy female controls. We also investigated how brain networks (connectomes) in each group responded to simulated neurodegeneration based on network attack analysis. Compared with controls, the breast cancer group demonstrated significantly lower fractional anisotropy, altered small-world connectome properties, lower brain network tolerance to systematic region (node), and connection (edge) attacks and significant cognitive impairment. Lower tolerance to network attack was associated with cognitive impairment in the breast cancer group. These findings provide further evidence of diffuse white matter pathology after breast cancer and extend the literature in this area with unique data demonstrating increased vulnerability of the post-breast cancer brain network to future neurodegenerative processes. PMID:26004016
Inference of brain pathway activities for Alzheimer's disease classification
Background Alzheimer's disease (AD) is a neurodegenerative and progressive disorder that results in brain malfunctions. Resting-state (RS) functional magnetic resonance imaging (fMRI) techniques have been successfully applied for quantifying brain activities of both Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients. Region-based approaches are widely utilized to classify patients from cognitively normal subjects (CN). Nevertheless, region-based approaches have a few limitations, reproducibility owing to selection of disease-specific brain regions, and heterogeneity of brain activities during disease progression. For coping with these issues, network-based approaches have been suggested in the field of molecular bioinformatics. In comparison with individual gene-based approaches, they acquired more accurate results in diverse disease classification, and reproducibility was confirmed by replication studies. In our work, we applied a similar methodology integrating brain pathway information into pathway activity inference, and permitting classification of both aMCI and AD patients based on pathway activities rather than single region activities. Results After aggregating the 59 brain pathways from literature, we estimated brain pathway activities by using exhaustive search algorithms between patients and cognitively normal subjects, and identified discriminatory pathways according to disease progression. We used three different data sets and each data set consists of two different groups. Our results show that the pathway-based approach (AUC = 0.89, 0.9, 0.75) outperformed the region-based approach (AUC = 0.69, 0.8, 0.68). Also, our approach provided enhanced diagnostic power achieving higher accuracy, sensitivity, and specificity (pathway-based approach: accuracy = 83%; sensitivity = 86%; specificity = 78%, region-based approach: accuracy = 74%; sensitivity = 78%; specificity = 76%). Conclusions We proposed a novel method inferring brain pathway activities for disease classification. Our approach shows better classification performance than region-based approach in four classification models. We expect that brain pathway-based approach would be helpful for precise classification of brain disorders, and provide new opportunities for uncovering disrupted brain pathways caused by disease. Moreover, discriminatory pathways between patients and cognitively normal subjects may facilitate the interpretation of functional alterations during disease progression. PMID:26044913
Pain reactivity in Alzheimer patients with different degrees of cognitive impairment and brain electrical activity deterioration
Fabrizio Benedetti; Claudia Arduino; Sergio Vighetti; Giovanni Asteggiano; Luisella Tarenzi; Innocenzo Rainero
Pain perception and autonomic responses to pain are known to be altered in dementia, although the mechanisms are poorly understood. We studied patients with Alzheimer's disease (AD) whose cognitive status was assessed through the Mini Mental State Examination test and whose brain electrical activity was measured by means of quantitative electroencephalography. After assessment of both cognitive impairment and brain electrical
Foetal Alcohol Spectrum Disorders and Alterations in Brain and Behaviour
Guerri, Consuelo; Bazinet, Alissa; Riley, Edward P.
The term 'Foetal Alcohol Spectrum Disorders (FASD)' refers to the range of disabilities that may result from prenatal alcohol exposure. This article reviews the effects of ethanol on the developing brain and its long-term structural and neurobehavioural consequences. Brain imaging, neurobehavioural and experimental studies demonstrate the devastating consequences of prenatal alcohol exposure on the developing central nervous system (CNS), identifying specific brain regions affected, the range of severity of effects and mechanisms involved. In particular, neuroimaging studies have demonstrated overall and regional volumetric and surface area reductions, abnormalities in the shape of particular brain regions, and reduced and increased densities for white and grey matter, respectively. Neurobehaviourally, FASD consists of a continuum of long-lasting deficits affecting multiple aspects of cognition and behaviour. Experimental studies have also provided evidence of the vulnerability of the CNS to the teratogenic effects of ethanol and have provided new insight on the influence of risk factors in the type and severity of observed brain abnormalities. Finally, the potential molecular mechanisms that underlie the neuroteratological effects of alcohol are discussed, with particular emphasis on the role of glial cells in long-term neurodevelopmental liabilities. PMID:19147799
Activities That Build the Young Child's Brain.
ERIC Educational Resources Information Center
Gellens, Suzanne R.
This book presents 350 classroom-tested activities for use with children to create an environment that will stimulate young children's brains. Designed to be used by families, classroom teachers, family childcare providers, or others caring for young children, the book includes information on current brain research and describes interest areas in…
Altered Expression of Diabetes-Related Genes in Alzheimer's Disease Brains: The Hisayama Study
Hokama, Masaaki; Oka, Sugako; Leon, Julio; Ninomiya, Toshiharu; Honda, Hiroyuki; Sasaki, Kensuke; Iwaki, Toru; Ohara, Tomoyuki; Sasaki, Tomio; LaFerla, Frank M.; Kiyohara, Yutaka; Nakabeppu, Yusaku
Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM. PMID:23595620
AQP4 gene deletion in mice does not alter blood-brain barrier integrity or brain morphology.
Saadoun, S; Tait, M J; Reza, A; Davies, D Ceri; Bell, B A; Verkman, A S; Papadopoulos, M C
The glial cell water channel aquaporin-4 (AQP4) plays an important role in brain edema, astrocyte migration, and neuronal excitability. Zhou et al. [Zhou J, Kong H, Hua X, Xiao M, Ding J, Hu G (2008) Altered blood-brain barrier integrity in adult aquaporin-4 knockout mice. Neuroreport 19:1-5] recently reported that AQP4 deletion significantly altered blood-brain barrier integrity and glial fibrillary acidic protein (GFAP) immunoreactivity in their AQP4 null mice. Here we describe a detailed characterization of baseline brain properties in our AQP4 null mice, including gross appearance, neuronal, astrocyte and oligodendrocyte characteristics, and blood-brain barrier integrity. Gross anatomical measurements included estimates of brain and ventricle size. Neurons, astrocytes and oligodendrocytes were assessed using the neuronal nuclear marker NeuN, the astrocyte marker GFAP, and the myelin stain Luxol Fast Blue. The blood-brain barrier was studied by electron microscopy and the horseradish peroxidase extravasation technique. There were no differences in brain and ventricle sizes between wild type and AQP4 null mice, nor were there differences in the cerebral cortical density of NeuN positive nuclei, perimicrovessel and glia limitans GFAP immunoreactivity, or the thickness and myelination of the corpus callosum. The ultrastructure of microvessels in the frontal cortex and caudate nucleus of wild type vs. AQP4 null mice was indistinguishable, with features including intact endothelial tight junctions, absence of perimicrovessel astrocyte foot process edema, and absence of horseradish peroxidase extravasation. In contrast to the report by Zhou et al. (2008), our data show that AQP4 deletion in mice does not produce major structural abnormalities in the brain. PMID:19345723
Alterations of Amino Acid Level in Depressed Rat Brain
Yang, Pei; Li, Xuechun; Tian, Jingchen; Jing, Fu; Qu, Changhai; Lin, Longfei; Zhang, Hui
Amino-acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. Several studies have demonstrated the potential of amino acids as a source of neuro-specific biomarkers could be used in future diagnosis of depression. Only partial amino acids such as glycine and asparagine were determined from certain parts of rats' brain included hippocampi and cerebral cortex in previous studies. However, according to systematic biology, amino acids in different area of brain are interacted and interrelated. Hence, the determination of 34 amino acids through entire rats' brain was conducted in this study in order to demonstrate more possibilities for biomarkers of depression by discovering other potential amino acids in more areas of rats' brain. As a result, 4 amino acids (L-aspartic acid, L-glutamine, taurine and ?-amino-n-butyric acid) among 34 were typically identified as potentially primary biomarkers of depression by data statistics. Meanwhile, an antidepressant called Fluoxetine was employed to verify other potential amino acids which were not identified by data statistics. Eventually, we found L-?-amino-adipic acid could also become a new potentially secondary biomarker of depression after drug validation. In conclusion, we suggested that L-aspartic acid, L-glutamine, taurine, ?-amino-n-butyric acid and L-?-amino-adipic acid might become potential biomarkers for future diagnosis of depression and development of antidepressant. PMID:25352755
Alterations of amino Acid level in depressed rat brain.
Yang, Pei; Li, Xuechun; Ni, Jian; Tian, Jingchen; Jing, Fu; Qu, Changhai; Lin, Longfei; Zhang, Hui
Amino-acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. Several studies have demonstrated the potential of amino acids as a source of neuro-specific biomarkers could be used in future diagnosis of depression. Only partial amino acids such as glycine and asparagine were determined from certain parts of rats' brain included hippocampi and cerebral cortex in previous studies. However, according to systematic biology, amino acids in different area of brain are interacted and interrelated. Hence, the determination of 34 amino acids through entire rats' brain was conducted in this study in order to demonstrate more possibilities for biomarkers of depression by discovering other potential amino acids in more areas of rats' brain. As a result, 4 amino acids (L-aspartic acid, L-glutamine, taurine and ?-amino-n-butyric acid) among 34 were typically identified as potentially primary biomarkers of depression by data statistics. Meanwhile, an antidepressant called Fluoxetine was employed to verify other potential amino acids which were not identified by data statistics. Eventually, we found L-?-amino-adipic acid could also become a new potentially secondary biomarker of depression after drug validation. In conclusion, we suggested that L-aspartic acid, L-glutamine, taurine, ?-amino-n-butyric acid and L-?-amino-adipic acid might become potential biomarkers for future diagnosis of depression and development of antidepressant. PMID:25352755
EEG Oscillatory States: Universality, Uniqueness and Specificity across Healthy-Normal, Altered and Pathological Brain Conditions
Fingelkurts, Alexander A.; Fingelkurts, Andrew A.
For the first time the dynamic repertoires and oscillatory types of local EEG states in 13 diverse conditions (examined over 9 studies) that covered healthy-normal, altered and pathological brain states were quantified within the same methodological and conceptual framework. EEG oscillatory states were assessed by the probability-classification analysis of short-term EEG spectral patterns. The results demonstrated that brain activity consists of a limited repertoire of local EEG states in any of the examined conditions. The size of the state repertoires was associated with changes in cognition and vigilance or neuropsychopathologic conditions. Additionally universal, optional and unique EEG states across 13 diverse conditions were observed. It was demonstrated also that EEG oscillations which constituted EEG states were characteristic for different groups of conditions in accordance to oscillations' functional significance. The results suggested that (a) there is a limit in the number of local states available to the cortex and many ways in which these local states can rearrange themselves and still produce the same global state and (b) EEG individuality is determined by varying proportions of universal, optional and unique oscillatory states. The results enriched our understanding about dynamic microstructure of EEG-signal. PMID:24505292
EEG oscillatory states: universality, uniqueness and specificity across healthy-normal, altered and pathological brain conditions.
Fingelkurts, Alexander A; Fingelkurts, Andrew A
For the first time the dynamic repertoires and oscillatory types of local EEG states in 13 diverse conditions (examined over 9 studies) that covered healthy-normal, altered and pathological brain states were quantified within the same methodological and conceptual framework. EEG oscillatory states were assessed by the probability-classification analysis of short-term EEG spectral patterns. The results demonstrated that brain activity consists of a limited repertoire of local EEG states in any of the examined conditions. The size of the state repertoires was associated with changes in cognition and vigilance or neuropsychopathologic conditions. Additionally universal, optional and unique EEG states across 13 diverse conditions were observed. It was demonstrated also that EEG oscillations which constituted EEG states were characteristic for different groups of conditions in accordance to oscillations' functional significance. The results suggested that (a) there is a limit in the number of local states available to the cortex and many ways in which these local states can rearrange themselves and still produce the same global state and (b) EEG individuality is determined by varying proportions of universal, optional and unique oscillatory states. The results enriched our understanding about dynamic microstructure of EEG-signal. PMID:24505292
Physical exercise improves brain cortex and cerebellum mitochondrial bioenergetics and alters apoptotic, dynamic and auto(mito)phagy markers.
Marques-Aleixo, I; Santos-Alves, E; Balça, M M; Rizo-Roca, D; Moreira, P I; Oliveira, P J; Magalhăes, J; Ascensăo, A
We here investigate the effects of two exercise modalities (endurance treadmill training-TM and voluntary free-wheel activity-FW) on the brain cortex and cerebellum mitochondrial bioenergetics, permeability transition pore (mPTP), oxidative stress, as well as on proteins involved in mitochondrial biogenesis, apoptosis, and quality control. Eighteen male rats were assigned to sedentary-SED, TM and FW groups. Behavioral alterations and ex vivo brain mitochondrial function endpoints were assessed. Proteins involved in oxidative phosphorylation (OXPHOS, including the adenine nucleotide translocator), oxidative stress markers and regulatory proteins (SIRT3, p66shc, UCP2, carbonyls, MDA, -SH, aconitase, Mn-SOD), as well as proteins involved in mitochondrial biogenesis (PGC1?, TFAM) were evaluated. Apoptotic signaling was measured through quantifying caspase 3, 8 and 9-like activities, Bax, Bcl2, CypD, and cofilin expression. Mitochondrial dynamics (Mfn1/2, OPA1 and DRP1) and auto(mito)phagy (LC3II, Beclin1, Pink1, Parkin, p62)-related proteins were also measured by Western blotting. Only the TM exercise group showed increased spontaneous alternation and exploratory activity. Both exercise regimens improved mitochondrial respiratory activity, increased OXPHOS complexes I, III and V subunits in both brain subareas and decreased oxidative stress markers. Increased resistance to mPTP and decreased apoptotic signaling were observed in the brain cortex from TM and in the cerebellum from TM and FW groups. Also, exercise increased the expression of proteins involved in mitochondrial biogenesis, autophagy and fusion, simultaneous with decreased expression of mitochondrial fission-related protein DRP1. In conclusion, physical exercise improves brain cortex and cerebellum mitochondrial function, decreasing oxidative stress and apoptotic related markers. It is also possible that favorable alterations in mitochondrial biogenesis, dynamics and autophagy signaling induced by exercise contributed to increased mitochondrial plasticity leading to a more robust phenotype. PMID:26116519
Maternal protein restriction early in rat pregnancy alters brain development in the progeny.
Gressens, P; Muaku, S M; Besse, L; Nsegbe, E; Gallego, J; Delpech, B; Gaultier, C; Evrard, P; Ketelslegers, J M; Maiter, D
We assessed the effects of a dietary protein restriction (5% vs. 20% casein in diet) initiated at conception and imposed during the first 2 weeks of rat gestation on postnatal brain development. At the end of the malnutrition period, protein-restricted animals exhibited significantly smaller fetal body weight and brain cortical thickness than controls. At birth and thereafter, body weight was normalized in the progeny. Similarly, brain weight and cytoarchitecture were normal in postnatal animals. In contrast, we observed, during the first 2 postnatal weeks, several abnormalities of brain development which affected all the studied areas for most of the studied parameters: (i) delayed astrocytogenesis as shown by a reduced GFAP staining; (ii) delayed production of hyaluronan in the extracellular matrix studied with binding of biotinylated hyaluronectin; (iii) abnormal neuronal differentiation as shown by reduced expression of MAP-5 and increased expression of MAP-1; (iv) abnormal synaptogenesis as shown by the increased expression of synaptophysin in the basal ganglia; (v) decreased programmed cell death. In adult prenatally protein-restricted animals, all the above parameters were normalized excepted MAP-1 labeling which remained high. In addition, we observed slight alterations of the ventilatory response to hypoxia in adult animals. The present study demonstrates that early protein malnutrition during embryonic development induces multiple, transient alterations of brain development. However, the almost complete normalization in adults of brain architecture and differentiation as well as our physiological data strongly suggest a remarkable plasticity of the developing brain following an early aggression. PMID:9370057
In situ biospectroscopic investigation of rapid ischemic and postmortem induced biochemical alterations in the rat brain.
Hackett, Mark J; Britz, Carter J; Paterson, Phyllis G; Nichol, Helen; Pickering, Ingrid J; George, Graham N
Rapid advances in imaging technologies have pushed novel spectroscopic modalities such as Fourier transform infrared spectroscopy (FTIR) and X-ray absorption spectroscopy (XAS) at the sulfur K-edge to the forefront of direct in situ investigation of brain biochemistry. However, few studies have examined the extent to which sample preparation artifacts confound results. Previous investigations using traditional analyses, such as tissue dissection, homogenization, and biochemical assay, conducted extensive research to identify biochemical alterations that occur ex vivo during sample preparation. In particular, altered metabolism and oxidative stress may be caused by animal death. These processes were a concern for studies using biochemical assays, and protocols were developed to minimize their occurrence. In this investigation, a similar approach was taken to identify the biochemical alterations that are detectable by two in situ spectroscopic methods (FTIR, XAS) that occur as a consequence of ischemic conditions created during humane animal killing. FTIR and XAS are well suited to study markers of altered metabolism such as lactate and creatine (FTIR) and markers of oxidative stress such as aggregated proteins (FTIR) and altered thiol redox (XAS). The results are in accordance with previous investigations using biochemical assays and demonstrate that the time between animal death and tissue dissection results in ischemic conditions that alter brain metabolism and initiate oxidative stress. Therefore, future in situ biospectroscopic investigations utilizing FTIR and XAS must take into consideration that brain tissue dissected from a healthy animal does not truly reflect the in vivo condition, but rather reflects a state of mild ischemia. If studies require the levels of metabolites (lactate, creatine) and markers of oxidative stress (thiol redox) to be preserved as close as possible to the in vivo condition, then rapid freezing of brain tissue via decapitation into liquid nitrogen, followed by chiseling the brain out at dry ice temperatures is required. PMID:25350866
Status epilepticus in the immature rodent brain alters the dynamics of autophagy.
Benz, Alexander Philipp; Niquet, Jerôme; Wasterlain, Claude Guy; Rami, Abdelhaq
There is considerable interest in defining the molecular pathways involved in seizure-induced neuronal death. Necrotic, apoptotic and anti-apoptotic signalling pathways are activated after status epilepticus (SE). Analyses of apoptosis and necrosis have been merely reported, however conditions of autophagic cell death with hallmarks of type 2 programmed cell death-morphology are relatively few. Autophagy is a highly regulated cellular mechanism for the bulk degradation of cytoplasmic contents which is involved in a variety of physiological and pathological conditions associated with neurological diseases. Our goal was to examine whether autophagy is implicated in the cell death machinery after SE. For this purpose, we used lithium-pilocarpine model of SE in 14-day-old rats and examined the dynamics in the expression of autophagic markers in the hippocampus in controls and in animals subjected to SE at 6, 24, and 48h after the insult. Protein levels of central components of the autophagic machinery were dramatically affected by SE with, however, altered dynamics, compared to controls. Levels of LC3, phospho-mTOR/mTOR, BAG3 and Hsp70 were significantly increased, whereas Beclin 1 levels remained unchanged after SE. The dynamics in the expression of Atg3, Atg5, Atg7, Atg14 and LAMP1 were slightly altered. The amount of SQSTM1/p62 underwent a dramatic and highly significant breakdown 48 h after the induction of SE. These results demonstrate for the first time that SE in the immature brain results in significant alterations of autophagy dynamics. There is a growing interest in the role of autophagy in neurodegeneration, and an emerging consensus that autophagy represents a double-edged sword, acting either as a prosurvival mechanism, or as part of a cell death pathway. PMID:24597603
Phylogenetic Origins of Early Alterations in Brain Region Proportions
Charvet, Christine J.; Sandoval, Alexis L.; Striedter, Georg F.
Adult galliform birds (e.g. chickens) exhibit a relatively small telencephalon and a proportionately large optic tectum compared with parrots and songbirds. We previously examined the embryonic origins of these adult species differences and found that the optic tectum is larger in quail than in parakeets and songbirds at early stages of development, prior to tectal neurogenesis onset. The aim of this study was to determine whether a proportionately large presumptive tectum is a primitive condition within birds or a derived feature of quail and other galliform birds. To this end, we examined embryonic brains of several avian species (emus, parrots, songbirds, waterfowl, galliform birds), reptiles (3 lizard species, alligators, turtles) and a monotreme (platypuses). Brain region volumes were estimated from serial Nissl-stained sections. We found that the embryos of galliform birds and lizards exhibit a proportionally larger presumptive tectum than all the other examined species. The presumptive tectum of the platypus is unusually small. The most parsimonious interpretation of these data is that the expanded embryonic tectum of lizards and galliform birds is a derived feature in both of these taxonomic groups. PMID:20332607
Copper deficiency alters the neurochemical profile of developing rat brain
Gybina, Anna A.; Tkac, Ivan; Prohaska, Joseph R.
Copper deficiency is associated with impaired brain development and mitochondrial dysfunction. Perinatal copper deficiency was produced in Holtzman rats. In vivo proton NMR spectroscopy was used to quantify 18 cerebellar and hippocampal metabolites on postnatal day 21 (P21). Copper status was evaluated in male copper-adequate (CuA) and copper-deficient (CuD) brothers at P19 and at P23, 2 days following NMR experiments, by metal and in vitro metabolite data. Compared to CuA pups, CuD pups had lower ascorbate concentration in both brain regions, confirming prior HPLC data. Both regions of CuD rats also had lower N-acetylaspartate levels consistent with delayed development or impaired mitochondrial function similar to prior work demonstrating elevated lactate and citrate. For other metabolites, the P21 neurochemical profile of CuD rats was remarkably similar to CuA rats but uniquely different from iron-deficient or chronic hypoxia models. Further research is needed to determine the neurochemical consequences of copper deficiency. PMID:19356314
Altered processing of sweet taste in the brain of diet soda drinkers
Green, Erin; Murphy, Claire
Artificially sweetened beverage consumption has been linked to obesity, and it has been hypothesized that considerable exposure to nonnutritive sweeteners may be associated with impaired energy regulation. The reward system plays an integral role in modulating energy intake, but little is known about whether habitual use of artificial sweetener (i.e., diet soda consumption) may be related to altered reward processing of sweet taste in the brain. To investigate this, we examined fMRI response after a 12-hour fast to sucrose (a nutritive sweetener) and saccharin (a nonnutritive sweetener) during hedonic evaluation in young adult diet soda drinkers and non-diet soda drinkers. Diet soda drinkers demonstrated greater activation to sweet taste in the dopaminergic midbrain (including ventral tegmental area) and right amygdala. Saccharin elicited a greater response in the right orbitofrontal cortex (Brodmann Area 47) relative to sucrose in non-diet soda drinkers. There was no difference in fMRI response to the nutritive or nonnutritive sweetener for diet soda drinkers. Within the diet soda drinkers, fMRI activation of the right caudate head in response to saccharin was negatively associated with the amount of diet sodas consumed per week; individuals who consumed a greater number of diet sodas had reduced caudate head activation. These findings suggest that there are alterations in reward processing of sweet taste in individuals who regularly consume diet soda, and this is associated with the degree of consumption. These findings may provide some insight into the link between diet soda consumption and obesity. PMID:22583859
The interconnectivity of mind, brain, and behavior in altered states of consciousness: focus on shamanism.
Wright, P A
This paper examines possible interconnections between mind, brain, and behavior in the area of shamanism and altered states of consciousness. It offers a neurophysiological theory of shamanic altered states of consciousness that integrates theories by Mandell, Persinger, Prince, Winkelman, and Wright. Topics include the shamanic call and temporal lobe phenomena, possible neurological correlates of shamanic ecstasy, and the neurophysiological roles of endorphins, plant substances, and genetic factors in shamanic altered states of consciousness. The difficulty of developing such a theory because of the complexity of human physiology and psychological experience and because of the paucity of neurophysiological data from the field is acknowledged. PMID:9359796
Perinatal iron and copper deficiencies alter neonatal rat circulating and brain thyroid hormone concentrations.
Bastian, Thomas W; Prohaska, Joseph R; Georgieff, Michael K; Anderson, Grant W
Copper (Cu), iron (Fe), and iodine/thyroid hormone (TH) deficiencies lead to similar defects in late brain development, suggesting that these micronutrient deficiencies share a common mechanism contributing to the observed derangements. Previous studies in rodents (postweanling and adult) and humans (adolescent and adult) indicate that Cu and Fe deficiencies affect the hypothalamic-pituitary-thyroid axis, leading to altered TH status. Importantly, however, relationships between Fe and Cu deficiencies and thyroidal status have not been assessed in the most vulnerable population, the developing fetus/neonate. We hypothesized that Cu and Fe deficiencies reduce circulating and brain TH levels during development, contributing to the defects in brain development associated with these deficiencies. To test this hypothesis, pregnant rat dams were rendered Cu deficient (CuD), FeD, or TH deficient from early gestation through weaning. Serum thyroxine (T(4)) and triiodothyronine (T(3)), and brain T(3) levels, were subsequently measured in postnatal d 12 (P12) pups. Cu deficiency reduced serum total T(3) by 48%, serum total T(4) by 21%, and whole-brain T(3) by 10% at P12. Fe deficiency reduced serum total T(3) by 43%, serum total T(4) by 67%, and whole-brain T(3) by 25% at P12. Brain mRNA analysis revealed that expression of several TH-responsive genes were altered in CuD or FeD neonates, suggesting that reduced TH concentrations were sensed by the FeD and CuD neonatal brain. These results indicate that at least some of the brain defects associated with neonatal Fe and Cu deficiencies are mediated through reductions in circulating and brain TH levels. PMID:20573724
Perinatal Iron and Copper Deficiencies Alter Neonatal Rat Circulating and Brain Thyroid Hormone Concentrations
Bastian, Thomas W.; Prohaska, Joseph R.; Georgieff, Michael K.; Anderson, Grant W.
Copper (Cu), iron (Fe), and iodine/thyroid hormone (TH) deficiencies lead to similar defects in late brain development, suggesting that these micronutrient deficiencies share a common mechanism contributing to the observed derangements. Previous studies in rodents (postweanling and adult) and humans (adolescent and adult) indicate that Cu and Fe deficiencies affect the hypothalamic-pituitary-thyroid axis, leading to altered TH status. Importantly, however, relationships between Fe and Cu deficiencies and thyroidal status have not been assessed in the most vulnerable population, the developing fetus/neonate. We hypothesized that Cu and Fe deficiencies reduce circulating and brain TH levels during development, contributing to the defects in brain development associated with these deficiencies. To test this hypothesis, pregnant rat dams were rendered Cu deficient (CuD), FeD, or TH deficient from early gestation through weaning. Serum thyroxine (T4) and triiodothyronine (T3), and brain T3 levels, were subsequently measured in postnatal d 12 (P12) pups. Cu deficiency reduced serum total T3 by 48%, serum total T4 by 21%, and whole-brain T3 by 10% at P12. Fe deficiency reduced serum total T3 by 43%, serum total T4 by 67%, and whole-brain T3 by 25% at P12. Brain mRNA analysis revealed that expression of several TH-responsive genes were altered in CuD or FeD neonates, suggesting that reduced TH concentrations were sensed by the FeD and CuD neonatal brain. These results indicate that at least some of the brain defects associated with neonatal Fe and Cu deficiencies are mediated through reductions in circulating and brain TH levels. PMID:20573724
Altered Emotional Interference Processing in Affective and Cognitive-Control Brain Circuitry in Major
. However, it is not yet clear whether this bias represents 1) impaired top-down cognitive control over, this bias may reflect an enhanced bottom-up response to emotional stimuli that dysregulates cognitiveAltered Emotional Interference Processing in Affective and Cognitive-Control Brain Circuitry
Verbal fluency deficits and altered lateralization of language brain areas in individuals genetically predisposed to schizophrenia
Tejas S Bhojraj; Alan N Francis; Rajaprabhakaran Rajarethinam; Shaun Eack; Shreedhar Kulkarni; Konasale M Prasad; Debra M Montrose; Diana Dworakowski; Vaibhav Diwadkar; Matcheri S Keshavan
Alterations of verbal fluency may correlate with deficits of gray matter volume and hemispheric lateralization of language brain regions like the pars triangularis (PT) in schizophrenia. Examining non-psychotic individuals at high genetic risk (HR) for schizophrenia may clarify if these deficits represent heritable trait markers or state dependent phenomena. We assessed adolescent and young adult HR subjects (N=60) and healthy
Altered neurochemical levels in the rat brain following chronic nicotine Sara Falasca a
Altered neurochemical levels in the rat brain following chronic nicotine treatment Sara Falasca Chronic nicotine Prefrontal cortex Dorsal striatum Hypothalamus A B S T R A C T Converging evidence shows that neurochemical systems are crucial mediators of nicotine dependence. Our present study evaluates the effect of 3
Iron Deficient and Manganese Supplemented Diets Alter Metals and Transporters in the Developing Rat Brain
Stephanie J. Garcia; Kristin Gellein; Tore Syversen; Michael Aschner
Manganese (Mn) neurotoxicity in adults can result in psycho- logical and neurological disturbances similar to Parkinson's disease, including extrapyramidal motor system defects and altered behaviors. Iron (Fe) deficiency is one of the most prevalent nutritional disorders in the world, affecting approximately 2 billion people, especially pregnant and lactating women, infants, toddlers, and adolescents. Fe deficiency can enhance brain Mn accumulation
Nanotools for Neuroscience and Brain Activity Mapping
Alivisatos, A. Paul; Andrews, Anne M.; Boyden, Edward S.; Chun, Miyoung; Church, George M.; Deisseroth, Karl; Donoghue, John P.; Fraser, Scott E.; Lippincott-Schwartz, Jennifer; Looger, Loren L.; Masmanidis, Sotiris; McEuen, Paul L.; Nurmikko, Arto V.; Park, Hongkun; Peterka, Darcy S.; Reid, Clay; Roukes, Michael L.; Scherer, Axel; Schnitzer, Mark; Sejnowski, Terrence J.; Shepard, Kenneth L.; Tsao, Doris; Turrigiano, Gina; Weiss, Paul S.; Xu, Chris; Yuste, Rafael; Zhuang, Xiaowei
Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function. PMID:23514423
Altered muscarinic and nicotinic receptor densities in cortical and subcortical brain regions in Parkinson's disease.
Lange, K W; Wells, F R; Jenner, P; Marsden, C D
Muscarinic and nicotinic cholinergic receptors and choline acetyltransferase activity were studied in postmortem brain tissue from patients with histopathologically confirmed Parkinson's disease and matched control subjects. Using washed membrane homogenates from the frontal cortex, hippocampus, caudate nucleus, and putamen, saturation analysis of specific receptor binding was performed for the total number of muscarinic receptors with [3H]quinuclidinyl benzilate, for muscarinic M1 receptors with [3H]pirenzepine, for muscarinic M2 receptors with [3H]oxotremorine-M, and for nicotinic receptors with (-)-[3H]nicotine. In comparison with control tissues, choline acetyl-transferase activity was reduced in the frontal cortex and hippocampus and unchanged in the caudate nucleus and putamen of parkinsonian patients. In Parkinson's disease the maximal binding site density for [3H]quinuclidinyl benzilate was increased in the frontal cortex and unaltered in the hippocampus, caudate nucleus, and putamen. Specific [3H]pirenzepine binding was increased in the frontal cortex, unaltered in the hippocampus, and decreased in the caudate nucleus and putamen. In parkinsonian patients Bmax values for specific [3H]oxotremorine-M binding were reduced in the cortex and unchanged in the hippocampus and striatum compared with controls. Maximal (-)-[3H]nicotine binding was reduced in both the cortex and hippocampus and unaltered in both the caudate nucleus and putamen. Alterations of the equilibrium dissociation constant were not observed for any ligand in any of the brain areas examined. The present results suggest that both the innominatocortical and the septohippocampal cholinergic systems degenerate in Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8417140
Brain-Specific Overexpression of Trace Amine-Associated Receptor 1 Alters Monoaminergic Neurotransmission and Decreases Sensitivity to Amphetamine
Revel, Florent G; Meyer, Claas A; Bradaia, Amyaouch; Jeanneau, Karine; Calcagno, Eleonora; André, Cédric B; Haenggi, Markus; Miss, Marie-Thérčse; Galley, Guido; Norcross, Roger D; Invernizzi, Roberto W; Wettstein, Joseph G; Moreau, Jean-Luc; Hoener, Marius C
Trace amines (TAs) such as ?-phenylethylamine, p-tyramine, or tryptamine are biogenic amines found in the brain at low concentrations that have been implicated in various neuropsychiatric disorders like schizophrenia, depression, or attention deficit hyperactivity disorder. TAs are ligands for the recently identified trace amine-associated receptor 1 (TAAR1), an important modulator of monoamine neurotransmission. Here, we sought to investigate the consequences of TAAR1 hypersignaling by generating a transgenic mouse line overexpressing Taar1 specifically in neurons. Taar1 transgenic mice did not show overt behavioral abnormalities under baseline conditions, despite augmented extracellular levels of dopamine and noradrenaline in the accumbens nucleus (Acb) and of serotonin in the medial prefrontal cortex. In vitro, this was correlated with an elevated spontaneous firing rate of monoaminergic neurons in the ventral tegmental area, dorsal raphe nucleus, and locus coeruleus as the result of ectopic TAAR1 expression. Furthermore, Taar1 transgenic mice were hyposensitive to the psychostimulant effects of amphetamine, as it produced only a weak locomotor activation and failed to alter catecholamine release in the Acb. Attenuating TAAR1 activity with the selective partial agonist RO5073012 restored the stimulating effects of amphetamine on locomotion. Overall, these data show that Taar1 brain overexpression causes hyposensitivity to amphetamine and alterations of monoaminergic neurotransmission. These observations confirm the modulatory role of TAAR1 on monoamine activity and suggest that in vivo the receptor is either constitutively active and/or tonically activated by ambient levels of endogenous agonist(s). PMID:22763617
Brain-specific overexpression of trace amine-associated receptor 1 alters monoaminergic neurotransmission and decreases sensitivity to amphetamine.
Revel, Florent G; Meyer, Claas A; Bradaia, Amyaouch; Jeanneau, Karine; Calcagno, Eleonora; André, Cédric B; Haenggi, Markus; Miss, Marie-Thérčse; Galley, Guido; Norcross, Roger D; Invernizzi, Roberto W; Wettstein, Joseph G; Moreau, Jean-Luc; Hoener, Marius C
Trace amines (TAs) such as ?-phenylethylamine, p-tyramine, or tryptamine are biogenic amines found in the brain at low concentrations that have been implicated in various neuropsychiatric disorders like schizophrenia, depression, or attention deficit hyperactivity disorder. TAs are ligands for the recently identified trace amine-associated receptor 1 (TAAR1), an important modulator of monoamine neurotransmission. Here, we sought to investigate the consequences of TAAR1 hypersignaling by generating a transgenic mouse line overexpressing Taar1 specifically in neurons. Taar1 transgenic mice did not show overt behavioral abnormalities under baseline conditions, despite augmented extracellular levels of dopamine and noradrenaline in the accumbens nucleus (Acb) and of serotonin in the medial prefrontal cortex. In vitro, this was correlated with an elevated spontaneous firing rate of monoaminergic neurons in the ventral tegmental area, dorsal raphe nucleus, and locus coeruleus as the result of ectopic TAAR1 expression. Furthermore, Taar1 transgenic mice were hyposensitive to the psychostimulant effects of amphetamine, as it produced only a weak locomotor activation and failed to alter catecholamine release in the Acb. Attenuating TAAR1 activity with the selective partial agonist RO5073012 restored the stimulating effects of amphetamine on locomotion. Overall, these data show that Taar1 brain overexpression causes hyposensitivity to amphetamine and alterations of monoaminergic neurotransmission. These observations confirm the modulatory role of TAAR1 on monoamine activity and suggest that in vivo the receptor is either constitutively active and/or tonically activated by ambient levels of endogenous agonist(s). PMID:22763617
Directional connectivity between frontal and posterior brain regions is altered with increasing concentrations of propofol.
Maksimow, Anu; Silfverhuth, Minna; Lĺngsjö, Jaakko; Kaskinoro, Kimmo; Georgiadis, Stefanos; Jääskeläinen, Satu; Scheinin, Harry
Recent studies using electroencephalography (EEG) suggest that alteration of coherent activity between the anterior and posterior brain regions might be used as a neurophysiologic correlate of anesthetic-induced unconsciousness. One way to assess causal relationships between brain regions is given by renormalized partial directed coherence (rPDC). Importantly, directional connectivity is evaluated in the frequency domain by taking into account the whole multichannel EEG, as opposed to time domain or two channel approaches. rPDC was applied here in order to investigate propofol induced changes in causal connectivity between four states of consciousness: awake (AWA), deep sedation (SED), loss (LOC) and return of consciousness (ROC) by gathering full 10/20 system human EEG data in ten healthy male subjects. The target-controlled drug infusion was started at low rate with subsequent gradual stepwise increases at 10 min intervals in order to carefully approach LOC (defined as loss of motor responsiveness to a verbal stimulus). The direction of the causal EEG-network connections clearly changed from AWA to SED and LOC. Propofol induced a decrease (p = 0.002-0.004) in occipital-to-frontal rPDC of 8-16 Hz EEG activity and an increase (p = 0.001-0.040) in frontal-to-occipital rPDC of 10-20 Hz activity on both sides of the brain during SED and LOC. In addition, frontal-to-parietal rPDC within 1-12 Hz increased in the left hemisphere at LOC compared to AWA (p = 0.003). However, no significant changes were detected between the SED and the LOC states. The observed decrease in back-to-front EEG connectivity appears compatible with impaired information flow from the posterior sensory and association cortices to the executive prefrontal areas, possibly related to decreased ability to perceive the surrounding world during sedation. The observed increase in the opposite (front-to-back) connectivity suggests a propofol concentration dependent association and is not directly related to the level of consciousness per se. PMID:25419791
Molecular substrates of altered axonal growth and brain connectivity in a mouse model of schizophrenia.
Mukai, Jun; Tamura, Makoto; Fénelon, Karine; Rosen, Andrew M; Spellman, Timothy J; Kang, Rujun; MacDermott, Amy B; Karayiorgou, Maria; Gordon, Joshua A; Gogos, Joseph A
22q11.2 deletion carriers show specific cognitive deficits, and ?30% of them develop schizophrenia. One of the disrupted genes is ZDHHC8, which encodes for a palmitoyltransferase. We show that Zdhhc8-deficient mice have reduced palmitoylation of proteins that regulate axonal growth and branching. Analysis of axonal projections of pyramidal neurons from both Zdhhc8-deficient and Df(16)A(+/-) mice, which model the 22q11.2 deletion, revealed deficits in axonal growth and terminal arborization, which can be prevented by reintroduction of active ZDHHC8 protein. Impaired terminal arborization is accompanied by a reduction in the strength of synaptic connections and altered functional connectivity and working memory. The effect of ZDHHC8 is mediated in part via Cdc42-dependent modulation of Akt/Gsk3? signaling at the tip of the axon and can be reversed by pharmacologically decreasing Gsk3? activity during postnatal brain development. Our findings provide valuable mechanistic insights into the cognitive and psychiatric symptoms associated with a schizophrenia-predisposing mutation. PMID:25913858
Targeting blood-brain barrier sphingolipid signaling reduces basal P-glycoprotein activity and improves drug delivery to the brain.
Cannon, Ronald E; Peart, John C; Hawkins, Brian T; Campos, Christopher R; Miller, David S
P-glycoprotein, an ATP-driven drug efflux pump, is a major obstacle to the delivery of small-molecule drugs across the blood-brain barrier and into the CNS. Here we test a unique signaling-based strategy to overcome this obstacle. We used a confocal microscopy-based assay with isolated rat brain capillaries to map a signaling pathway that within minutes abolishes P-glycoprotein transport activity without altering transporter protein expression or tight junction permeability. This pathway encompasses elements of proinflammatory- (TNF-?) and sphingolipid-based signaling. Critical to this pathway was signaling through sphingosine-1-phosphate receptor 1 (S1PR1). In brain capillaries, S1P acted through S1PR1 to rapidly and reversibly reduce P-glycoprotein transport activity. Sphingosine reduced transport by a sphingosine kinase-dependent mechanism. Importantly, fingolimod (FTY720), a S1P analog recently approved for treatment of multiple sclerosis, also rapidly reduced P-glycoprotein activity; similar effects were found with the active, phosphorylated metabolite (FTY720P). We validated these findings in vivo using in situ brain perfusion in rats. Administration of S1P, FTY720, or FTY729P increased brain uptake of three radiolabeled P-glycoprotein substrates, (3)H-verapamil (threefold increase), (3)H-loperamide (fivefold increase), and (3)H-paclitaxel (fivefold increase); blocking S1PR1 abolished this effect. Tight junctional permeability, measured as brain (14)C-sucrose accumulation, was not altered. Therefore, targeting signaling through S1PR1 at the blood-brain barrier with the sphingolipid-based drugs, FTY720 or FTY720P, can rapidly and reversibly reduce basal P-glycoprotein activity and thus improve delivery of small-molecule therapeutics to the brain. PMID:22949658
N-Acetylcysteine Ameliorates Carbofuraninduced Alterations in Lipid Composition and Activity of Membrane Bound Enzymes
Amit Kamboj; Ravi Kiran; Rajat Sandhir
The present work investigates the protective effects of N-acetylcysteine (NAC) on carbofuran-induced alterations in lipid\\u000a composition and activity of membrane bound enzymes (Na+-K+-ATPase and Ca2+-ATPase) in the rat brain. Animals were exposed to carbofuran at a dose of 1 mg\\/kg body weight, orally, for a period of 28\\u000a days. A significant increase in lipid peroxidation in terms of TBARS was
Alterations in the sense of time, space, and body in the mindfulness-trained brain: a neurophenomenologically-guided MEG study
Berkovich-Ohana, Aviva; Dor-Ziderman, Yair; Glicksohn, Joseph; Goldstein, Abraham
Meditation practice can lead to what have been referred to as "altered states of consciousness."One of the phenomenological characteristics of these states is a joint alteration in the sense of time, space, and body. Here, we set out to study the unique experiences of alteration in the sense of time and space by collaborating with a select group of 12 long-term mindfulness meditation (MM) practitioners in a neurophenomenological setup, utilizing first-person data to guide the neural analyses. We hypothesized that the underlying neural activity accompanying alterations in the sense of time and space would be related to alterations in bodily processing. The participants were asked to volitionally bring about distinct states of "Timelessness" (outside time) and "Spacelessness" (outside space) while their brain activity was recorded by MEG. In order to rule out the involvement of attention, memory, or imagination, we used control states of "Then" (past) and "There" (another place). MEG sensors evidencing alterations in power values were identified, and the brain regions underlying these changes were estimated via spatial filtering (beamforming). Particularly, we searched for similar neural activity hypothesized to underlie both the state of "Timelessness" and "Spacelessness." The results were mostly confined to the theta band, and showed that: (1) the "Then"/"There" overlap yielded activity in regions related to autobiographic memory and imagery (right posterior parietal lobule (PPL), right precentral/middle frontal gyrus (MFG), bilateral precuneus); (2) "Timelessness"/"Spacelessness" conditions overlapped in a different network, related to alterations in the sense of the body (posterior cingulate, right temporoparietal junction (TPJ), cerebellum); and (3) phenomenologically-guided neural analyses enabled us to dissociate different levels of alterations in the sense of the body. This study illustrates the utility of employing experienced contemplative practitioners within a neurophenomenological setup for scientifically characterizing a self-induced altered sense of time, space and body, as well as the importance of theta activity in relation with these altered states. PMID:24348455
Alterations in the sense of time, space, and body in the mindfulness-trained brain: a neurophenomenologically-guided MEG study.
Berkovich-Ohana, Aviva; Dor-Ziderman, Yair; Glicksohn, Joseph; Goldstein, Abraham
Meditation practice can lead to what have been referred to as "altered states of consciousness."One of the phenomenological characteristics of these states is a joint alteration in the sense of time, space, and body. Here, we set out to study the unique experiences of alteration in the sense of time and space by collaborating with a select group of 12 long-term mindfulness meditation (MM) practitioners in a neurophenomenological setup, utilizing first-person data to guide the neural analyses. We hypothesized that the underlying neural activity accompanying alterations in the sense of time and space would be related to alterations in bodily processing. The participants were asked to volitionally bring about distinct states of "Timelessness" (outside time) and "Spacelessness" (outside space) while their brain activity was recorded by MEG. In order to rule out the involvement of attention, memory, or imagination, we used control states of "Then" (past) and "There" (another place). MEG sensors evidencing alterations in power values were identified, and the brain regions underlying these changes were estimated via spatial filtering (beamforming). Particularly, we searched for similar neural activity hypothesized to underlie both the state of "Timelessness" and "Spacelessness." The results were mostly confined to the theta band, and showed that: (1) the "Then"/"There" overlap yielded activity in regions related to autobiographic memory and imagery (right posterior parietal lobule (PPL), right precentral/middle frontal gyrus (MFG), bilateral precuneus); (2) "Timelessness"/"Spacelessness" conditions overlapped in a different network, related to alterations in the sense of the body (posterior cingulate, right temporoparietal junction (TPJ), cerebellum); and (3) phenomenologically-guided neural analyses enabled us to dissociate different levels of alterations in the sense of the body. This study illustrates the utility of employing experienced contemplative practitioners within a neurophenomenological setup for scientifically characterizing a self-induced altered sense of time, space and body, as well as the importance of theta activity in relation with these altered states. PMID:24348455
The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: further development of a rodent model of autism spectrum disorders
Gastrointestinal symptoms and altered blood phospholipid profiles have been reported in patients with autism spectrum disorders (ASD). Most of the phospholipid analyses have been conducted on the fatty acid composition of isolated phospholipid classes following hydrolysis. A paucity of information exists on how the intact phospholipid molecular species are altered in ASD. We applied ESI/MS to determine how brain and blood intact phospholipid species were altered during the induction of ASD-like behaviors in rats following intraventricular infusions with the enteric bacterial metabolite propionic acid. Animals were infused daily for 8?days, locomotor activity assessed, and animals killed during the induced behaviors. Propionic acid infusions increased locomotor activity. Lipid analysis revealed treatment altered 21 brain and 30 blood phospholipid molecular species. Notable alterations were observed in the composition of brain SM, diacyl mono and polyunsaturated PC, PI, PS, PE, and plasmalogen PC and PE molecular species. These alterations suggest that the propionic acid rat model is a useful tool to study aberrations in lipid metabolism known to affect membrane fluidity, peroxisomal function, gap junction coupling capacity, signaling, and neuroinflammation, all of which may be associated with the pathogenesis of ASD. PMID:22747852
Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions
Weiland, N.G.; Wise, P.M.
Norepinephrine regulates the proestrous and estradiol-induced LH surge by binding to alpha 1-adrenergic receptors. The density of alpha 1-receptors may be regulated by estradiol, photoperiod, and noradrenergic neuronal activity. We wished to determine whether alpha 1-receptors exhibit a diurnal rhythm in ovariectomized and/or estradiol-treated female rats, whether estradiol regulates alpha 1-receptors in those areas of brain involved with LH secretion and/or sexual behavior, and whether the concentrations of alpha-receptors vary inversely relative to previously reported norepinephrine turnover patterns. Young female rats, maintained on a 14:10 light-dark cycle were ovariectomized. One week later, half of them were outfitted sc with Silastic capsules containing estradiol. Groups of animals were decapitated 2 days later at 0300, 1000, 1300, 1500, 1800, and 2300 h. Brains were removed, frozen, and sectioned at 20 micron. Sections were incubated with (/sup 3/H)prazosin in Tris-HCl buffer, washed, dried, and exposed to LKB Ultrofilm. The densities of alpha 1-receptors were quantitated using a computerized image analysis system. In ovariectomized rats, the density of alpha 1-receptors exhibited a diurnal rhythm in the suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), and pineal gland. In SCN and MPN, receptor concentrations were lowest during the middle of the day and rose to peak levels at 1800 h. In the pineal gland, the density of alpha 1-receptors was lowest at middark phase, rose to peak levels before lights on, and remained elevated during the day. Estradiol suppressed the density of alpha 1 binding sites in the SCN, MPN, median eminence, ventromedial nucleus, and the pineal gland but had no effect on the lateral septum. Estrogen treatment altered the rhythm of receptor densities in MPN, median eminence, and the pineal gland.
Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging
Gazdzinski, Lisa M.; Cormier, Kyle [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada)] [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Lu, Fred G. [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada)] [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada); Lerch, Jason P. [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada) [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada); Wong, C. Shun [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada) [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada); Department of Radiation Oncology, University of Toronto, Toronto (Canada); Nieman, Brian J., E-mail: firstname.lastname@example.com [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada)
Purpose: The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal magnetic resonance imaging (MRI). Methods and Materials: Female C57Bl/6 mice received a whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation and at 3 time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation. Results: Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared with controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone. Conclusions: MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after pediatric cranial irradiation.
Do brain tissue transplants alter personal identity? Inadequacies of some "standard" arguments.
Northoff, G
Currently, brain tissue transplantations are being developed as a clinical-therapeutic tool in neurodegenerative diseases such as Parkinson's or Alzheimer's disease. From an ethical point of view, distinguishing between the preservation and an alteration of personal identity seems to be central to determining the scope for further application of brain tissue transplantation therapy. The purpose of this article is to review "standard" arguments which are used on the one hand by proponents to prove preservation of personal identity and by opponents on the other hand to prove that brain tissue transplantation results in an altered personal identity. Proponents and opponents are shown to use the same arguments, albeit with different presuppositions. These presuppositions concern the meaning of the term "identity", either numerical or qualitative, the definition of brain identity, either structurally or functionally, and the relationship between mental states, psychological functions and neurophysiological properties as criteria for personal identity. Furthermore the respective neurophysiological, clinical and philosophical evidence for the different presuppositions are discussed. It is concluded that evaluation of personal identity in brain tissue transplantation should not only rely on the "standard" arguments but, additionally, neurophysiological, clinical and philosophical implications should be discussed. PMID:8798941
Structural analysis of brain ganglioside acetylation patterns in mice with altered ganglioside biosynthesis.
Mlinac, Kristina; Fabris, Dragana; Vukeli?, Zeljka; Rožman, Marko; Heffer, Marija; Bognar, Svjetlana Kalanj
Gangliosides are sialylated membrane glycosphingolipids especially abundant in mammalian brain tissue. Sialic acid O-acetylation is one of the most common structural modifications of gangliosides which considerably influences their chemical properties. In this study, gangliosides extracted from brain tissue of mice with altered ganglioside biosynthesis (St8sia1 null and B4galnt1 null mice) were structurally characterized and their acetylation pattern was analyzed. Extracted native and alkali-treated gangliosides were resolved by high performance thin layer chromatography. Ganglioside mixtures as well as separated individual ganglioside fractions were further analyzed by tandem mass spectrometry. Several O-acetylated brain ganglioside species were found in knockout mice, not present in the wild-type mice. To the best of our knowledge this is the first report on the presence of O-acetylated GD1a in St8sia1 null mice and O-acetylated GM3 species in B4galnt1 null mice. In addition, much higher diversity of abnormally accumulated brain ganglioside species regarding the structure of ceramide portion was observed in knockout versus wild-type mice. Obtained findings indicate that the diversity of brain ganglioside structures as well as acetylation patterns in mice with altered ganglioside biosynthesis, is even higher than previously reported. Further investigation is needed in order to explore the effects of acetylation on ganglioside interactions with other molecules and consequently the physiological role of acetylated ganglioside species. PMID:24140892
Peroxisome Proliferator-Activated Receptor beta/delta in the Brain: Facts and Hypothesis.
Hall, M G; Quignodon, Laure; Desvergne, Béatrice
peroxisome proliferator-activated receptors (PPARs) are nuclear receptors acting as lipid sensors. Besides its metabolic activity in peripheral organs, the PPAR beta/delta isotype is highly expressed in the brain and its deletion in mice induces a brain developmental defect. Nevertheless, exploration of PPARbeta action in the central nervous system remains sketchy. The lipid content alteration observed in PPARbeta null brains and the positive action of PPARbeta agonists on oligodendrocyte differentiation, a process characterized by lipid accumulation, suggest that PPARbeta acts on the fatty acids and/or cholesterol metabolisms in the brain. PPARbeta could also regulate central inflammation and antioxidant mechanisms in the damaged brain. Even if not fully understood, the neuroprotective effect of PPARbeta agonists highlights their potential benefit to treat various acute or chronic neurological disorders. In this perspective, we need to better understand the basic function of PPARbeta in the brain. This review proposes different leads for future researches. PMID:19009042
Brain activation during a social attribution task in adolescents with moderate to severe traumatic brain injury
Scheibel, Randall S.; Newsome, Mary R.; Wilde, Elisabeth A.; McClelland, Michelle M.; Hanten, Gerri; Krawczyk, Daniel C.; Cook, Lori G.; Chu, Zili D.; Vásquez, Ana C.; Yallampalli, Ragini; Lin, Xiaodi; Hunter, Jill V.; Levin, Harvey S.
The ability to make accurate judgments about the mental states of others, sometimes referred to as theory of mind (ToM), is often impaired following traumatic brain injury (TBI), and this deficit may contribute to problems with interpersonal relationships. The present study used an animated social attribution task (SAT) with functional magnetic resonance imaging (fMRI) to examine structures mediating ToM in adolescents with moderate to severe TBI. The study design also included a comparison group of matched, typically developing (TD) adolescents. The TD group exhibited activation within a number of areas that are thought to be relevant to ToM, including the medial prefrontal and anterior cingulate cortex, fusiform gyrus, and posterior temporal and parietal areas. The TBI subjects had significant activation within many of these same areas, but their activation was generally more intense and excluded the medial prefrontal cortex. Exploratory regression analyses indicated a negative relation between ToM-related activation and measures of white matter integrity derived from diffusion tensor imaging, while there was also a positive relation between activation and lesion volume. These findings are consistent with alterations in the level and pattern of brain activation that may be due to the combined influence of diffuse axonal injury and focal lesions. PMID:21777109
Modulation of Brain Activity during Phonological Familiarization
ERIC Educational Resources Information Center
Majerus, S.; Van der Linden, M.; Collette, F.; Laureys, S.; Poncelet, M.; Degueldre, C.; Delfiore, G.; Luxen, A.; Salmon, E.
We measured brain activity in 12 adults for the repetition of auditorily presented words and nonwords, before and after repeated exposure to their phonological form. The nonword phoneme combinations were either of high (HF) or low (LF) phonotactic frequency. After familiarization, we observed, for both word and nonword conditions, decreased…
Brain Activity with Reading Sentences and Emoticons
Masahide Yuasa; Keiichi Saito; Naoki Mukawa
In this paper, we describe a person's brain activity when he\\/she sees an emoticon at the end of a sentence. An emoticon consists of some characters that resemble the human face and expresses a sender's emotion. With the help of a computer network, we use e-mail, messenger, avatars and so on, in order to convey what we wish to, to
Social reinforcement can regulate localized brain activity
Krystyna A. MathiakYury; Yury Koush; Miriam Dyck; Tilman J. Gaber; Eliza Alawi; Florian D. Zepf; Mikhail Zvyagintsev; Klaus Mathiak
Social learning is essential for adaptive behavior in humans. Neurofeedback based on functional magnetic resonance imaging\\u000a (fMRI) trains control over localized brain activity. It can disentangle learning processes at the neural level and thus investigate\\u000a the mechanisms of operant conditioning with explicit social reinforcers. In a pilot study, a computer-generated face provided\\u000a a positive feedback (smiling) when activity in the
Electromagnetic imaging of dynamic brain activity
Mosher, J.; Leahy, R. [University of Southern California, Los Angeles, CA (United States). Dept. of Electrical Engineering; Lewis, P.; Lewine, J.; George, J. [Los Alamos National Lab., NM (United States); Singh, M. [University of Southern California, Los Angeles, CA (United States). Dept. of Radiology
Neural activity in the brain produces weak dynamic electromagnetic fields that can be measured by an array of sensors. Using a spatio-temporal modeling framework, we have developed a new approach to localization of multiple neural sources. This approach is based on the MUSIC algorithm originally developed for estimating the direction of arrival of signals impinging on a sensor array. We present applications of this technique to magnetic field measurements of a phantom and of a human evoked somatosensory response. The results of the somatosensory localization are mapped onto the brain anatomy obtained from magnetic resonance images.
Electromagnetic imaging of dynamic brain activity
Mosher, J.; Leahy, R. (University of Southern California, Los Angeles, CA (United States). Dept. of Electrical Engineering); Lewis, P.; Lewine, J.; George, J. (Los Alamos National Lab., NM (United States)); Singh, M. (University of Southern California, Los Angeles, CA (United States). Dept. of Radiology)
Neural activity in the brain produces weak dynamic electromagnetic fields that can be measured by an array of sensors. Using a spatio-temporal modeling framework, we have developed a new approach to localization of multiple neural sources. This approach is based on the MUSIC algorithm originally developed for estimating the direction of arrival of signals impinging on a sensor array. We present applications of this technique to magnetic field measurements of a phantom and of a human evoked somatosensory response. The results of the somatosensory localization are mapped onto the brain anatomy obtained from magnetic resonance images.
Ketogenic Diet Prevents Alterations in Brain Metabolism in Young but not Adult Rats after Traumatic Brain Injury
Prins, Mayumi L.; Hovda, David A.; Harris, Neil G.
Abstract Previous studies have shown that the change of cerebral metabolic rate of glucose (CMRglc) in response to traumatic brain injury (TBI) is different in young (PND35) and adult rats (PND70), and that prolonged ketogenic diet treatment results in histological and behavioral neuroprotection only in younger rat brains. However, the mechanism(s) through which ketones act in the injured brain and the biochemical markers of their action remain unknown. Therefore, the current study was initiated to: 1) determine the effect of injury on the neurochemical profile in PND35 compared to PND70 rats; and 2) test the effect of early post-injury administration of ketogenic diet on brain metabolism in PND35 versus PND70 rats. The data show that alterations in energy metabolites, amino acid, and membrane metabolites were not evident in PND35 rats on standard diet until 24?h after injury, when the concentration of most metabolites was reduced from sham-injured values. In contrast, acute, but transient deficits in energy metabolism were measured at 6?h in PND70 rats, together with deficits in N-acetylaspartate that endured until 24?h. Administration of a ketogenic diet resulted in significant increases in plasma ?-hydroxybutyrate (?OHB) levels. Similarly, brain ?OHB levels were significantly elevated in all injured rats, but were elevated by 43% more in PND35 rats compared to PND70 rats. As a result, ATP, creatine, and phosphocreatine levels at 24?h after injury were significantly improved in the ketogenic PND35 rats, but not in the PND70 group. The improvement in energy metabolism in the PND35 brains was accompanied by the recovery of NAA and reduction of lactate levels, as well as amelioration of the deficits of other amino acids and membrane metabolites. These results indicate that the PND35 brains are more resistant to the injury, indicated by a delayed deficit in energy metabolism. Moreover, the younger brains revert to ketones metabolism more quickly than do the adult brains, resulting in better neurochemical and cerebral metabolic recovery after injury. PMID:21635175
Prenatal stress alters microglial development and distribution in postnatal rat brain
Beatriz Gómez-González; Alfonso Escobar
Stress affects microglial function and viability during adulthood and early postnatal life; however, it is unknown whether\\u000a stress to the pregnant dam might alter offspring microglia. The effects of prenatal stress on microglial development and distribution\\u000a in the postnatal brain were studied using Wistar rats. Prenatal stress consisting of 20 min of forced swimming occurred on\\u000a embryonic days 10–20. On postnatal
Classification of whole brain fMRI activation patterns
Balc?, Serdar Kemal
Functional magnetic resonance imaging (fMRI) is an imaging technology which is primarily used to perform brain activation studies by measuring neural activity in the brain. It is an interesting question whether patterns ...
Do Exercise and Physical Activity Protect the Brain?
... Do Exercise and Physical Activity Protect the Brain? Exercise and physical activity have many benefits. Studies show ... what about brain health? Some studies suggest that exercise also may play a role in reducing risk ...
Altered structure of cortical sulci in gilles de la Tourette syndrome: Further support for abnormal brain development.
Muellner, Julia; Delmaire, Christine; Valabrégue, Romain; Schüpbach, Michael; Mangin, Jean-François; Vidailhet, Marie; Lehéricy, Stéphane; Hartmann, Andreas; Worbe, Yulia
Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by the presence of motor and vocal tics. We hypothesized that patients with this syndrome would present an aberrant pattern of cortical formation, which could potentially reflect global alterations of brain development. Using 3 Tesla structural neuroimaging, we compared sulcal depth, opening, and length and thickness of sulcal gray matter in 52 adult patients and 52 matched controls. Cortical sulci were automatically reconstructed and identified over the whole brain, using BrainVisa software. We focused on frontal, parietal, and temporal cortical regions, in which abnormal structure and functional activity were identified in previous neuroimaging studies. Partial correlation analysis with age, sex, and treatment as covariables of noninterest was performed amongst relevant clinical and neuroimaging variables in patients. Patients with Gilles de la Tourette syndrome showed lower depth and reduced thickness of gray matter in the pre- and post-central as well as superior, inferior, and internal frontal sulci. In patients with associated obsessive-compulsive disorder, additional structural changes were found in temporal, insular, and olfactory sulci. Crucially, severity of tics and of obsessive-compulsive disorder measured by Yale Global Tic severity scale and Yale-Brown Obsessive-Compulsive scale, respectively, correlated with structural sulcal changes in sensorimotor, temporal, dorsolateral prefrontal, and middle cingulate cortical areas. Patients with Gilles de la Tourette syndrome displayed an abnormal structural pattern of cortical sulci, which correlated with severity of clinical symptoms. Our results provide further evidence of abnormal brain development in GTS. PMID:25820811
Words in the brain: lexical determinants of word-induced brain activity
Coulson, Seana
Words in the brain: lexical determinants of word-induced brain activity Lee Osterhout*, Mark Allen Abstract Many studies have shown that open- and closed-class words elicit different patterns of brain. Introduction Is the brain response to words determined primarily by their linguistic functions
Temporal organization of ongoing brain activity
NASA Astrophysics Data System (ADS)
Lombardi, F.; de Arcangelis, L.
Ongoing brain activity results from the mutual interaction of hundred billions non-linear units and represents a significant part of the overall brain activity. Although its complex dynamics has been widely investigated, a large number of fundamental questions are still open, many of them concerning its temporal structure. Why does a certain population of neurons fires synchronously? Are these synchronized bursts following each other randomly or are they correlated according to some organizing principle? Far from addressing the fundamental problem of its functions, in the present article we focus on the problem of temporal correlations of ongoing cortical activity. We first overview the major features of its temporal structure and review recent experimental results, with particular emphasis on alternative approaches inspired in the theory of stochastic processes; then we introduce a neuronal network model inspired in self organized criticality and compare numerical results with experimental findings.
Irritable Bowel Syndrome in female patients is associated with alterations in structural brain networks
Labus, Jennifer; Dinov, Ivo D.; Jiang, Zhiguo; Ashe-McNalley, Cody; Zamanyan, Alen; Shi, Yonggang; Hong, Jui-Yang; Gupta, Arpana; Tillisch, Kirsten; Ebrat, Bahar; Hobel, Sam; Gutman, Boris A.; Joshi, Shantanu; Thompson, Paul M.; Toga, Arthur W.; Mayer, Emeran A.
Alterations in gray matter (GM) density/ volume and cortical thickness (CT) have been demonstrated in small and heterogeneous samples of subjects with different chronic pain syndromes, including irritable bowel syndrome (IBS). Aggregating across 7 structural neuroimaging studies conducted at UCLA between August 2006 and April 2011, we examined group differences in regional GM volume in 201 predominantly premenopausal female subjects (82 IBS, mean age: 32 ± 10 SD, 119 Healthy Controls [HCs], 30± 10 SD). Applying graph theoretical methods and controlling for total brain volume, global and regional properties of large-scale structural brain networks were compared between IBS and HC groups. Relative to HCs, the IBS group had lower volumes in bilateral superior frontal gyrus, bilateral insula, bilateral amygdala, bilateral hippocampus, bilateral middle orbital frontal gyrus, left cingulate, left gyrus rectus, brainstem, and left putamen. Higher volume was found for the left postcentral gyrus. Group differences were no longer significant for most regions when controlling for Early Trauma Inventory global score with the exception of the right amygdala and the left post central gyrus. No group differences were found for measures of global and local network organization. Compared to HCs, the right cingulate gyrus and right thalamus were identified as significantly more critical for information flow. Regions involved in endogenous pain modulation and central sensory amplification were identified as network hubs in IBS. Overall, evidence for central alterations in IBS was found in the form of regional GM volume differences and altered global and regional properties of brain volumetric networks. PMID:24076048
Cigarette Smoke Induces DNA Damage and Alters Base-Excision Repair and Tau Levels in the Brain of Neonatal Mice
La Maestra, Sebastiano; Kisby, Glen E.; Micale, Rosanna T.; Johnson, Jessica; Kow, Yoke W.; Bao, Gaobin; Sheppard, Clayton; Stanfield, Sarah; Tran, Huong; Woltjer, Randall L.; D'Agostini, Francesco; Steele, Vernon E.; De Flora, Silvio
The prenatal and perinatal periods of brain development are especially vulnerable to insults by environmental agents. Early life exposure to cigarette smoke (CS), which contains both genotoxicants and oxidants, is considered an important risk factor for both neurodevelopmental and neurodegenerative disorders. Yet, little is known regarding the underlying pathogenetic mechanisms. In the present study, neonatal Swiss ICR (CD-1) albino mice were exposed to various concentrations of CS for 4 weeks and the brain examined for lipid peroxides, DNA damage, base-excision repair (BER) enzymes, apoptosis, and levels of the microtubule protein tau. CS induced a dose-dependent increase in both malondialdehyde and various types of DNA damage, including single-strand breaks, double-strand breaks, and DNA-protein cross-links. However, the CS-induced DNA damage in the brain returned to basal levels 1 week after smoking cessation. CS also modulated the activity and distribution of the BER enzymes 8-oxoguanine-DNA-glycosylase (OGG1) and apyrimidinic/apurinic endonuclease (APE1) in several brain regions. Normal tau (i.e., three-repeat tau, 3R tau) and various pathological forms of tau were also measured in the brain of CS-exposed neonatal mice, but only 3R tau and tau phosphorylated at serine 199 were significantly elevated. The oxidative stress, genomic dysregulation, and alterations in tau metabolism caused by CS during a critical period of brain development could explain why CS is an important risk factor for both neurodevelopmental and neurodegenerative disorders appearing in later life. PMID:21778470
Using Brain Electrical Activity Mapping to Diagnose Learning Disabilities.
ERIC Educational Resources Information Center
Torello, Michael, W.; Duffy, Frank H.
Cognitive neuroscience assumes that measurement of brain electrical activity should relate to cognition. Brain Electrical Activity Mapping (BEAM), a non-invasive technique, is used to record changes in activity from one brain area to another and is 80 to 90 percent successful in classifying subjects as dyslexic or normal. (MT)
Melatonin Alters Age-Related Changes in Transcription Factors and Kinase Activation
Bondy, Stephen C.; Li, Huihui; Zhou, Jun; Wu, Meixia; Bailey, Jason A.; Lahiri, Debomoy K.
considered as a marker of brain immune activation. In accordthat of the brain, which has only intrinsic immune activity.immune-related transcription factors with age and their responses to melatonin vary between brain and
Cerebral blood volume alterations in the perilesional areas in the rat brain after traumatic brain injury—comparison with behavioral outcome
Riikka Immonen; Taneli Heikkinen; Leena Tähtivaara; Antti Nurmi; Taina-Kaisa Stenius; Jukka Puoliväli; Tinka Tuinstra; Amie L Phinney; Bernard Van Vliet; Juha Yrjänheikki; Olli Gröhn
In the traumatic brain injury (TBI) the initial impact causes both primary injury, and launches secondary injury cascades. One consequence, and a factor that may contribute to these secondary changes and functional outcome, is altered hemodynamics. The relative cerebral blood volume (CBV) changes in rat brain after severe controlled cortical impact injury were characterized to assess their interrelations with motor
Estradiol and ER? agonists enhance recognition memory, and DPN, an ER? agonist, alters brain monoamines
Jacome, Luis F.; Gautreaux, Claris; Inagaki, Tomoko; Mohan, Govini; Alves, Stephen; Lubbers, Laura S.; Luine, Victoria
Effects of estradiol benzoate (EB), ER?-selective agonist, propyl pyrazole triol (PPT) and ER?-selective agonists, diarylpropionitrile (DPN) and Compound 19 (C-19) on memory were investigated in OVX rats using object recognition (OR) and placement (OP) memory tasks. Treatments were acute (behavior 4 h later) or sub chronic (daily injections for 2 days with behavior 48 h later). Objects were explored in sample trials (T1), and discrimination between sample (old) and new object/location in recognition trials (T2) was examined after 2–4 h inter-trial delays. Subjects treated sub chronically with EB, DPN, and C-19, but not PPT, discriminated between old and new objects and objects in old and new locations, suggesting that, at these doses and duration of treatments, estrogenic interactions with ER? contributes to enhancements in recognition memory. Acute injections of DPN, but not PPT, immediately after T1, also enhanced discrimination for both tasks (C19 was not investigated). Effects of EB, DPN and PPT on anxiety and locomotion, measured on elevated plus maze and open field, did not appear to account for the mnemonic enhancements. Monoamines and metabolites were measured following DPN treatment in subjects that did not receive behavioral testing. DPN was associated with alterations in monoamines in several brain areas: indexed by the metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), or the MHPG/norepinephrine (NE) ratio, NE activity was increased by 60–130% in the prefrontal cortex (PFC) and ventral hippocampus, and NE activity was decreased by 40–80% in the v. diagonal bands and CA1. Levels of the dopamine (DA) metabolite, homovanillic acid (HVA), increased 100% in the PFC and decreased by 50% in the dentate gyrus following DPN treatment. The metabolite of serotonin, 5-hydroxyindole acetic acid (5-HIAA), was increased in the PFC and CA3, by approximately 20%. No monoaminergic changes were noted in striatum or medial septum. Results suggest that ER? mediates sub chronic and acute effects of estrogens on recognition memory and that memory enhancements by DPN may occur, in part, through alterations in monoaminergic containing systems primarily in PFC and hippocampus. PMID:20828630
Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain
Lee, Won Hee [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States); Warrington, Junie P.; Sonntag, William E. [Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Lee, Yong Woo, E-mail: email@example.com [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States); Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States)
Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy {gamma}-rays or a fractionated dose of 40 Gy {gamma}-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.
The novel antiepileptic drug levetiracetam (ucb L059) induces alterations in GABA metabolism and turnover in discrete areas of rat brain and reduces neuronal activity in substantia nigra pars reticulata
Wolfgang Löscher; Dagmar Hönack; Petra Bloms-Funke
Levetiracetam ((S)-?-ethyl -2-oxo-pyrrolidine acetamide, ucb L059) is a novel anticonvulsant drug presently in clinical development. Its mechanism of action is unknown although a recently reported novel specific binding site for [3H]levetiracetam, unique to brain, may be involved. This binding site has not yet been characterized, but some evidence suggested a possibly indirect interaction with the GABA system. We therefore examined
Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility
Coleman, Leon Garland; Liu, Wen; Oguz, Ipek; Styner, Martin; Crews, Fulton T.
Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28–37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility. PMID:24275185
Ionizing radiation alters beta-endorphin-like immunoreactivity in brain but not blood
Mickley, G.A.; Stevens, K.E.; Moore, G.H.; Deere, W.; White, G.A.; Gibbs, G.L.; Mueller, G.P.
Previous behavioral and pharmacological studies have implicated endorphins in radiation-induced locomotor hyperactivity of the C57BL/6J mouse. However, the endogenous opiate(s) responsible for this behavioral change have not been identified. The present study measured beta-endorphin-like immunoreactivity (beta-END-LI) in brain, blood, and combined brain and pituitary samples from irradiated and sham-irradiated C57BL/6J mice. After radiation exposure, levels of beta-END-LI decreased significantly in the brain. A similar, but not statistically significant, decline was measured in combined brain and pituitary samples. Concentrations of blood beta-END-LI were not changed by irradiation. These radiogenic changes in beta-END-LI are in some ways similar to those observed after other stresses. However, radiation-induced locomotor hyperactivity may be mediated more by alterations of beta-END-LI in the brain than in the periphery. Other endogenous opiate systems may also contribute to this behavioral change in the C57BL/6J mouse.
Alterations in muscle activation patterns during robotic-assisted walking
Joseph M. Hidler; Anji E. Wall
Objective. The goal of this study was to compare the muscle activation patterns in various major leg muscles during treadmill ambulation with those exhibited during robotic-assisted walking. Background. Robotic devices are now being integrated into neurorehabilitation programs with promising results. The influence of these devices on altering naturally occurring muscle activation patterns utilized during walking have not been quantified. Methods.
Does mental exertion alter maximal muscle activation?
Rozand, Vianney; Pageaux, Benjamin; Marcora, Samuele M.; Papaxanthis, Charalambos; Lepers, Romuald
Mental exertion is known to impair endurance performance, but its effects on neuromuscular function remain unclear. The purpose of this study was to test the hypothesis that mental exertion reduces torque and muscle activation during intermittent maximal voluntary contractions of the knee extensors. Ten subjects performed in a randomized order three separate mental exertion conditions lasting 27 min each: (i) high mental exertion (incongruent Stroop task), (ii) moderate mental exertion (congruent Stroop task), (iii) low mental exertion (watching a movie). In each condition, mental exertion was combined with 10 intermittent maximal voluntary contractions of the knee extensor muscles (one maximal voluntary contraction every 3 min). Neuromuscular function was assessed using electrical nerve stimulation. Maximal voluntary torque, maximal muscle activation and other neuromuscular parameters were similar across mental exertion conditions and did not change over time. These findings suggest that mental exertion does not affect neuromuscular function during intermittent maximal voluntary contractions of the knee extensors. PMID:25309404
The Physiochemistry of Capped Nanosilver Predicts Its Biological Activity in Rat Brain Endothelial Cells (REBEC4)
The "capping" or coating of nanosilver (nanoAg) extends its potency by limiting its oxidation and aggregation and stabilizing its size and shape. The ability of such coated nanoAg to alter the permeability and activate oxidative stress pathways in rat brain endothelia...
Alteration of spontaneous neuronal activity in young adults with non-clinical depressive symptoms.
Wei, Xinhua; Shen, Huicong; Ren, Jiliang; Liu, Wenhua; Yang, Ruimeng; Liu, Jun; Wu, Hongzhen; Xu, Xiangdong; Lai, Lisha; Hu, Jiani; Pan, Xiaoping; Jiang, Xinqing
Non-clinical depressive symptoms (nCDSs) are highly prevalent in young adults and may be associated with the risk of developing full-fledged depressive disorders. However, the neural basis underlying nCDSs remains unknown. To explore the alteration of spontaneous brain activity in individuals with nCDSs compared with healthy controls (HCs), we investigated resting-state brain activity using the amplitude of low-frequency fluctuations (ALFF) in subjects with nCDSs (n=17) and HCs (n=20). All subjects were drawn from a sample of 1105 college students participating in a survey assessing depressive symptoms. We determined that nCDSs can lead to reduced ALFF in the right ventral lateral prefrontal cortex (VLPFC) and right dorsolateral prefrontal cortex (DLPFC) and to increased ALFF in the left fusiform, left posterior cerebellum, right cuneus, left inferior parietal lobule, right supramarginal gyrus and bilateral precuneus. In addition, with respect to Beck Depression Inventory (BDI) scores and ALFF values in subjects with nCDSs, a positive correlation was discovered in the right DLPFC, while a negative correlation was identified in left posterior cerebellum and bilateral precuneus after correction. These results indicate that nCDSs are characterized by altered spontaneous activity in several important functional regions. We suggest that altered ALFFs in the right DLPFC, left posterior cerebellum and bilateral precuneus may be biomarkers that are related to the pathophysiology of nCDSs in young adults. PMID:26004037
Iron deficient and manganese supplemented diets alter metals and transporters in the developing rat brain.
Garcia, Stephanie J; Gellein, Kristin; Syversen, Tore; Aschner, Michael
Manganese (Mn) neurotoxicity in adults can result in psychological and neurological disturbances similar to Parkinson's disease, including extrapyramidal motor system defects and altered behaviors. Iron (Fe) deficiency is one of the most prevalent nutritional disorders in the world, affecting approximately 2 billion people, especially pregnant and lactating women, infants, toddlers, and adolescents. Fe deficiency can enhance brain Mn accumulation even in the absence of excess Mn in the environment or the diet. To assess the neurochemical interactions of dietary Fe deficiency and excess Mn during development, neonatal rats were exposed to either a control diet, a low-Fe diet (ID), or a low-Fe diet supplemented with Mn (IDMn) via maternal milk during the lactation period (postnatal days [PN] 4-21). In PN21 pups, both the ID and IDMn diets produced changes in blood parameters characteristic of Fe deficiency: decreased hemoglobin (Hb) and plasma Fe, increased plasma transferrin (Tf), and total iron binding capacity (TIBC). Treated ID and IDMn dams also had decreased Hb throughout lactation and ID dams had decreased plasma Fe and increased Tf and TIBC on PN21. Both ID and IDMn pups had decreased Fe and increased copper brain levels; in addition, IDMn pups also had increased brain levels of several other essential metals including Mn, chromium, zinc, cobalt, aluminum, molybdenum, and vanadium. Concurrent with altered concentrations of metals in the brain, transport proteins divalent metal transporter-1 and transferrin receptor were increased. No significant changes were determined for the neurotransmitters gamma aminobutyric acid and glutamate. The results of this study confirm that there is homeostatic relationship among several essential metals in the brain and not simply between Fe and Mn. PMID:17060373
Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice
S H Fatemi; E S Emamian; R W Sidwell; D A Kist; J M Stary; J A Earle; P Thuras
Epidemiological reports describe a strong association between prenatal human influenza viral infection and later development of schizophrenia. Postmodern human brain studies, however, indicate a lack of gliosis in schizophrenic brains presumably secondary to absence of glial cells during the second trimester viral infection in utero. We hypothesized that human influenza infection in day 9 pregnant mice would alter the expression
Neutralization of endogenous digitalis-like compounds alters catecholamines metabolism in the brain and elicits anti-depressive behavior.
Goldstein, Inbal; Lax, Elad; Gispan-Herman, Iris; Ovadia, Haim; Rosen, Haim; Yadid, Gal; Lichtstein, David
Depressive disorders are among the world's greatest public health problems. Na(+), K(+)-ATPase is the established receptor for the steroidal digitalis-like compounds (DLC). Alteration in brain Na(+), K(+)-ATPase and DLC have been detected in depressive disorders raising the hypothesis of their involvement in these pathology. The present study was designed to further elaborate this hypothesis by investigating the behavioral and biochemical consequences of neutralization in brain DLC activity attained by anti-ouabain antibodies administrations, in normal Sprague-Dawley (SD) and in the Flinders Sensitive Line (FSL) of genetically depressed rats. Chronic i.c.v. administration of anti-ouabain antibodies to FSL rats elicited anti-depressive behavior. Administration of anti-ouabain antibodies intracerebroventriculary (i.c.v.) to SD rats significantly changed the levels of catecholamines and their metabolites in the hippocampus, ventral tegmentum and nucleus accumbence. These results are in accordance with the notion that endogenous DLC may be involved in the manifestation of depressive disorders and suggests that alteration in their levels may be of significant therapeutic value. PMID:21700431
Minocycline protects against oxidative damage and alters energy metabolism parameters in the brain of rats subjected to chronic mild stress.
Réus, Gislaine Z; Abelaira, Helena M; Maciel, Amanda L; Dos Santos, Maria Augusta B; Carlessi, Anelise S; Steckert, Amanda V; Ferreira, Gabriela K; De Prá, Samira D; Streck, Emilio L; Macędo, Danielle S; Quevedo, Joăo
Studies have been suggested that minocycline can be a potential new agent for the treatment of depression. In addition, both oxidative stress and energy metabolism present an important role in pathophysiology of depression. So, the present study was aimed to evaluate the effects of minocycline on stress oxidative parameters and energy metabolism in the brain of adult rats submitted to the chronic mild stress protocol (CMS). After CMS Wistar, both stressed animals as controls received twice ICV injection of minocycline (160 ?g) or vehicle. The oxidative stress and energy metabolism parameters were assessed in the prefrontal cortex (PF), hippocampus (HIP), amygdala (AMY) and nucleus accumbens (Nac). Our findings showed that stress induced an increase on protein carbonyl in the PF, AMY and NAc, and mynocicline injection reversed this alteration. The TBARS was increased by stress in the PF, HIP and NAc, however, minocycline reversed the alteration in the PF and HIP. The Complex I was incrased in AMY by stress, and minocycline reversed this effect, however reduced Complex I activity in the NAc; Complex II reduced in PF and AMY by stress or minocycline; the Complex II-III increased in the HIP in stress plus minocycline treatment and in the NAc with minocycline; in the PF and HIP there were a reduced in Complex IV with stress and minocycline. The creatine kinase was reduced in AMY and NAc with stress and minocycline. In conclusion, minocycline presented neuroprotector effects by reducing oxidative damage and regulating energy metabolism in specific brain areas. PMID:25112549
Effects of cranial electrotherapy stimulation on resting state brain activity
Feusner, Jamie D; Madsen, Sarah; Moody, Teena D; Bohon, Cara; Hembacher, Emily; Bookheimer, Susan Y; Bystritsky, Alexander
Cranial electrotherapy stimulation (CES) is a U.S. Food and Drug Administration (FDA)-approved treatment for insomnia, depression, and anxiety consisting of pulsed, low-intensity current applied to the earlobes or scalp. Despite empirical evidence of clinical efficacy, its mechanism of action is largely unknown. The goal was to characterize the acute effects of CES on resting state brain activity. Our primary hypothesis was that CES would result in deactivation in cortical and subcortical regions. Eleven healthy controls were administered CES applied to the earlobes at subsensory thresholds while being scanned with functional magnetic resonance imaging in the resting state. We tested 0.5- and 100-Hz stimulation, using blocks of 22 sec "on" alternating with 22 sec of baseline (device was "off"). The primary outcome measure was differences in blood oxygen level dependent data associated with the device being on versus baseline. The secondary outcome measures were the effects of stimulation on connectivity within the default mode, sensorimotor, and fronto-parietal networks. Both 0.5- and 100-Hz stimulation resulted in significant deactivation in midline frontal and parietal regions. 100-Hz stimulation was associated with both increases and decreases in connectivity within the default mode network (DMN). Results suggest that CES causes cortical brain deactivation, with a similar pattern for high- and low-frequency stimulation, and alters connectivity in the DMN. These effects may result from interference from high- or low-frequency noise. Small perturbations of brain oscillations may therefore have significant effects on normal resting state brain activity. These results provide insight into the mechanism of action of CES, and may assist in the future development of optimal parameters for effective treatment. PMID:22741094
Brain mechanical property measurement using MRE with intrinsic activation
NASA Astrophysics Data System (ADS)
Weaver, John B.; Pattison, Adam J.; McGarry, Matthew D.; Perreard, Irina M.; Swienckowski, Jessica G.; Eskey, Clifford J.; Lollis, S. Scott; Paulsen, Keith D.
Many pathologies alter the mechanical properties of tissue. Magnetic resonance elastography (MRE) has been developed to noninvasively characterize these quantities in vivo. Typically, small vibrations are induced in the tissue of interest with an external mechanical actuator. The resulting displacements are measured with phase contrast sequences and are then used to estimate the underlying mechanical property distribution. Several MRE studies have quantified brain tissue properties. However, the cranium and meninges, especially the dura, are very effective at damping externally applied vibrations from penetrating deeply into the brain. Here, we report a method, termed 'intrinsic activation', that eliminates the requirement for external vibrations by measuring the motion generated by natural blood vessel pulsation. A retrospectively gated phase contrast MR angiography sequence was used to record the tissue velocity at eight phases of the cardiac cycle. The velocities were numerically integrated via the Fourier transform to produce the harmonic displacements at each position within the brain. The displacements were then reconstructed into images of the shear modulus based on both linear elastic and poroelastic models. The mechanical properties produced fall within the range of brain tissue estimates reported in the literature and, equally important, the technique yielded highly reproducible results. The mean shear modulus was 8.1 kPa for linear elastic reconstructions and 2.4 kPa for poroelastic reconstructions where fluid pressure carries a portion of the stress. Gross structures of the brain were visualized, particularly in the poroelastic reconstructions. Intra-subject variability was significantly less than the inter-subject variability in a study of six asymptomatic individuals. Further, larger changes in mechanical properties were observed in individuals when examined over time than when the MRE procedures were repeated on the same day. Cardiac pulsation, termed intrinsic activation, produces sufficient motion to allow mechanical properties to be recovered. The poroelastic model is more consistent with the measured data from brain at low frequencies than the linear elastic model. Intrinsic activation allows MRE to be performed without a device shaking the head so the patient notices no differences between it and the other sequences in an MR examination.
Investigating the physiology of brain activation with MRI
NASA Astrophysics Data System (ADS)
Buxton, Richard B.; Uludag, Kamil; Dubowitz, David J.
Functional magnetic resonance imaging (fMRI) has become a powerful tool for investigating the working human brain based on the blood oxygenation level dependent (BOLD) effect on the MR signal. However, despite the widespread use of fMRI techniques for mapping brain activation, the basic physiological mechanisms underlying the observed signal changes are still poorly understood. Arterial spin labeling (ASL) techniques, which measure cerebral blood flow (CBF) and the BOLD effect simultaneously, provide a useful tool for investigating these physiological questions. In this paper, recent results of studies manipulating the baseline CBF both pharmacologically and physiologically will be discussed. These data are consistent with a feed-forward mechanism of neurovascular coupling, and suggest that the CBF change itself may be a more robust reflection of neural activity changes than the BOLD effect. Consistent with these data, a new thermodynamic hypothesis is proposed for the physiological function of CBF regulation: maintenance of the [O2]/[CO2] concentration ratio at the mitochondria in order to preserve the free energy available from oxidative metabolism. A kinetic model based on this hypothesis provides a reasonable quantitative description of the CBF changes associated with neural activity and altered blood gases (CO2 and O2).
Postnatal disruption of the disintegrin/metalloproteinase ADAM10 in brain causes epileptic seizures, learning deficits, altered spine morphology, and defective synaptic functions.
Prox, Johannes; Bernreuther, Christian; Altmeppen, Hermann; Grendel, Jasper; Glatzel, Markus; D'Hooge, Rudi; Stroobants, Stijn; Ahmed, Tariq; Balschun, Detlef; Willem, Michael; Lammich, Sven; Isbrandt, Dirk; Schweizer, Michaela; Horré, Katrien; De Strooper, Bart; Saftig, Paul
The metalloproteinase ADAM10 is of importance for Notch-dependent cortical brain development. The protease is tightly linked with ?-secretase activity toward the amyloid precursor protein (APP) substrate. Increasing ADAM10 activity is suggested as a therapy to prevent the production of the neurotoxic amyloid ? (A?) peptide in Alzheimer's disease. To investigate the function of ADAM10 in postnatal brain, we generated Adam10 conditional knock-out (A10cKO) mice using a CaMKII?-Cre deleter strain. The lack of ADAM10 protein expression was evident in the brain cortex leading to a reduced generation of sAPP? and increased levels of sAPP? and endogenous A? peptides. The A10cKO mice are characterized by weight loss and increased mortality after weaning associated with seizures. Behavioral comparison of adult mice revealed that the loss of ADAM10 in the A10cKO mice resulted in decreased neuromotor abilities and reduced learning performance, which were associated with altered in vivo network activities in the hippocampal CA1 region and impaired synaptic function. Histological and ultrastructural analysis of ADAM10-depleted brain revealed astrogliosis, microglia activation, and impaired number and altered morphology of postsynaptic spine structures. A defect in spine morphology was further supported by a reduction of the expression of NMDA receptors subunit 2A and 2B. The reduced shedding of essential postsynaptic cell adhesion proteins such as N-Cadherin, Nectin-1, and APP may explain the postsynaptic defects and the impaired learning, altered network activity, and synaptic plasticity of the A10cKO mice. Our study reveals that ADAM10 is instrumental for synaptic and neuronal network function in the adult murine brain. PMID:23926248
The thalamus and brainstem act as key hubs in alterations of human brain network connectivity induced by mild propofol sedation
Gili, Tommaso; Saxena, Neeraj; Diukova, Ana; Murphy, Kevin; Hall, Judith E; Wise, Richard G
Despite their routine use during surgical procedures, no consensus has yet been reached on the precise mechanisms by which hypnotic anesthetic agents produce their effects. Molecular, animal and human studies have suggested disruption of thalamocortical communication as a key component of anesthetic action at the brain systems level. Here, we used the anesthetic agent, propofol, to modulate consciousness and to evaluate differences in the interactions of remote neural networks during altered consciousness. We investigated the effects of propofol, at a dose that produced mild sedation without loss of consciousness, on spontaneous cerebral activity of fifteen healthy volunteers using functional magnetic resonance imaging (fMRI), exploiting oscillations (<0.1 Hz) in BOLD signal across functionally connected brain regions. We considered the data as a graph, or complex network of nodes and links and used eigenvector centrality (EC) to characterise brain network properties. The EC mapping of fMRI data in healthy humans under propofol mild sedation, demonstrated a decrease of centrality of the thalamus versus an increase of centrality within the pons of the brainstem, highlighting the important role of these two structures in regulating consciousness. Specifically, the decrease of thalamus centrality results from its disconnection from a widespread set of cortical and subcortical regions, while the increase of brainstem centrality may be a consequence of its increased influence, in the mildly sedated state, over a few highly central cortical regions key to the default mode network such as the posterior and anterior cingulate cortices. PMID:23447611
Alterations in blood-brain barrier function by morphine and methamphetamine.
Sharma, Hari Shanker; Ali, Syed F
The possibility that stress associated with morphine and amphetamine administration or withdrawal will influence the blood-brain barrier (BBB) and brain dysfunction was examined in a rodent model. Repeated daily administration of morphine (10 mg/kg, i.p.) resulted in drug dependence in rats on the sixth day and onwards. Measurement of the BBB permeability to large molecule tracers normally bound to proteins, e.g., Evans blue albumin and radioiodine (([131])Iodine) did not show any leakage on the 12th day of drug dependence. On the other hand, spontaneous withdrawal of morphine on day 1 resulted in profound stress symptoms. These symptoms were much more intense on the second day of morphine withdrawal. Alterations in the BBB to protein tracers were seen in several regions of the brain. This increase in BBB to protein tracers was most pronounced on the second day of morphine withdrawal. These rats also exhibited abnormal neuronal, glial and stress protein, the heat-shock protein 72 kD (HSP-72 kD) response. On the other hand, acute administration of methamphetamine (40 mg/kg, i.p.) in mice resulted in marked extravasation of endogenous serum protein as seen with increased expression of albumin immunohistochemistry. These observations suggest that psychostimulants and associated stress are capable to influence the brain function, probably through modifying the BBB function, not reported earlier. PMID:17105918
Brain activation during phonological and semantic processing of Chinese characters in deaf signers.
Li, Yanyan; Peng, Danling; Liu, Li; Booth, James R; Ding, Guosheng
Previous studies found altered brain function in deaf individuals reading alphabetic orthographies. However, it is not known whether similar alterations of brain function are characteristic of non-alphabetic writing systems and whether alterations are specific to certain kinds of lexical tasks. Here we examined differences in brain activation between Chinese congenitally deaf individuals (CD) and hearing controls (HC) during character reading tasks requiring phonological and semantic judgments. For both tasks, we found that CD showed less activation than HC in left inferior frontal gyrus, but greater activation in several right hemisphere regions including inferior frontal gyrus, angular gyrus, and inferior temporal gyrus. Although many group differences were similar across tasks, greater activation in right middle frontal gyrus was more pronounced for the rhyming compared to the meaning task. Finally, within the deaf individuals better performance on the rhyming task was associated with less activation in right inferior parietal lobule and angular gyrus. Our results in Chinese CD are broadly consistent with previous studies in alphabetic languages suggesting greater engagement of inferior frontal gyrus and inferior parietal cortex for reading that is largely independent of task, with the exception of right middle frontal gyrus for phonological processing. The brain behavior correlations potentially indicate that CD that more efficiently use the right hemisphere are better readers. PMID:24795593
Regulation of brain aromatase activity in rats
Roselli, C.E.; Ellinwood, W.E.; Resko, J.A.
The distribution and regulation of aromatase activity in the adult rat brain with a sensitive in vitro assay that measures the amount of /sup 3/H/sub 2/O formed during the conversion of (1 beta-/sup 3/H)androstenedione to estrone. The rate of aromatase activity in the hypothalamus-preoptic area (HPOA) was linear with time up to 1 h, and with tissue concentrations up to 5 mgeq/200 microliters incubation mixture. The enzyme demonstrated a pH optimum of 7.4 and an apparent Michaelis-Menten constant (Km) of 0.04 microns. The greatest amount of aromatase activity was found in amygdala and HPOA from intact male rats. The hippocampus, midbrain tegmentum, cerebral cortex, cerebellum, and anterior pituitary all contained negligible enzymatic activity. Castration produced a significant decrease in aromatase activity in the HPOA, but not in the amygdala or cerebral cortex. The HPOAs of male rats contained significantly greater aromatase activity than the HPOAs of female rats. In females, this enzyme activity did not change during the estrous cycle or after ovariectomy. Administration of testosterone to gonadectomized male and female rats significantly enhanced HPOA aromatase activities to levels approximating those found in HPOA from intact males. Therefore, the results suggest that testosterone, or one of its metabolites, is a major steroidal regulator of HPOA aromatase activity in rats.
Multifunctional Roles of Enolase in Alzheimer Disease Brain: Beyond Altered Glucose Metabolism
Butterfield, D. Allan; Bader Lange, Miranda L.
Enolase enzymes are abundantly expressed, cytosolic carbon-oxygen lyases known for their role in glucose metabolism. Recently, enolase has been shown to possess a variety of different regulatory functions, beyond glycolysis and gluconeogenesis, associated with hypoxia, ischemia, and Alzheimer disease (AD). AD is an age-associated neurodegenerative disorder characterized pathologically by elevated oxidative stress and subsequent damage to proteins, lipids, and nucleic acids, appearance of neurofibrillary tangles and senile plaques, and loss of synapse and neuronal cells. It is unclear if development of a hypometabolic environment is a consequence of or contributes to AD pathology, since there is not only a significant decline in brain glucose levels in AD, but also there is an increase in proteomics identified oxidatively modified glycolytic enzymes that are rendered inactive, including enolase. Previously, our laboratory identified ?-enolase as one the most frequently up-regulated and oxidatively modified proteins in amnestic mild cognitive impairment (MCI), early-onset AD (EOAD), and AD. However, the glycolytic conversion of 2-phosphoglycerate to phosphoenolpyruvate catalyzed by enolase does not directly produce ATP or NADH; therefore it is surprising that, among all glycolytic enzymes, ?-enolase was one of only two glycolytic enzymes consistently up-regulated from MCI to AD. These findings suggest enolase is involved with more than glucose metabolism in AD brain, but may possess other functions, normally necessary to preserve brain function. This review examines potential altered function(s) of brain enolase in MCI, EOAD, and AD, alterations that may contribute to the biochemical, pathological, clinical characteristics, and progression of this dementing disorder. PMID:19780894
Long-duration transcutaneous electric acupoint stimulation alters small-world brain functional networks.
Zhang, Yue; Jiang, Yin; Glielmi, Christopher B; Li, Longchuan; Hu, Xiaoping; Wang, Xiaoying; Han, Jisheng; Zhang, Jue; Cui, Cailian; Fang, Jing
Acupuncture, which is recognized as an alternative and complementary treatment in Western medicine, has long shown efficiencies in chronic pain relief, drug addiction treatment, stroke rehabilitation and other clinical practices. The neural mechanism underlying acupuncture, however, is still unclear. Many studies have focused on the sustained effects of acupuncture on healthy subjects, yet there are very few on the topological organization of functional networks in the whole brain in response to long-duration acupuncture (longer than 20 min). This paper presents a novel study on the effects of long-duration transcutaneous electric acupoint stimulation (TEAS) on the small-world properties of brain functional networks. Functional magnetic resonance imaging was used to construct brain functional networks of 18 healthy subjects (9 males and 9 females) during the resting state. All subjects received both TEAS and minimal TEAS (MTEAS) and were scanned before and after each stimulation. An altered functional network was found with lower local efficiency and no significant change in global efficiency for healthy subjects after TEAS, while no significant difference was observed after MTEAS. The experiments also showed that the nodal efficiencies in several paralimbic/limbic regions were altered by TEAS, and those in middle frontal gyrus and other regions by MTEAS. To remove the psychological effects and the baseline, we compared the difference between diffTEAS (difference between after and before TEAS) and diffMTEAS (difference between after and before MTEAS). The results showed that the local efficiency was decreased and that the nodal efficiencies in frontal gyrus, orbitofrontal cortex, anterior cingulate gyrus and hippocampus gyrus were changed. Based on those observations, we conclude that long-duration TEAS may modulate the short-range connections of brain functional networks and also the limbic system. PMID:23684242
Alterations in Brain Inflammation, Synaptic Proteins, and Adult Hippocampal Neurogenesis during Epileptogenesis in Mice Lacking Synapsin2
Chugh, Deepti; Ali, Idrish; Bakochi, Anahita; Bahonjic, Elma; Etholm, Lars; Ekdahl, Christine T.
Synapsins are pre-synaptic vesicle-associated proteins linked to the pathogenesis of epilepsy through genetic association studies in humans. Deletion of synapsins causes an excitatory/inhibitory imbalance, exemplified by the epileptic phenotype of synapsin knockout mice. These mice develop handling-induced tonic-clonic seizures starting at the age of about 3 months. Hence, they provide an opportunity to study epileptogenic alterations in a temporally controlled manner. Here, we evaluated brain inflammation, synaptic protein expression, and adult hippocampal neurogenesis in the epileptogenic (1 and 2 months of age) and tonic-clonic (3.5-4 months) phase of synapsin 2 knockout mice using immunohistochemical and biochemical assays. In the epileptogenic phase, region-specific microglial activation was evident, accompanied by an increase in the chemokine receptor CX3CR1, interleukin-6, and tumor necrosis factor-?, and a decrease in chemokine keratinocyte chemoattractant/ growth-related oncogene. Both post-synaptic density-95 and gephyrin, scaffolding proteins at excitatory and inhibitory synapses, respectively, showed a significant up-regulation primarily in the cortex. Furthermore, we observed an increase in the inhibitory adhesion molecules neuroligin-2 and neurofascin and potassium chloride co-transporter KCC2. Decreased expression of ?-aminobutyric acid receptor-? subunit and cholecystokinin was also evident. Surprisingly, hippocampal neurogenesis was reduced in the epileptogenic phase. Taken together, we report molecular alterations in brain inflammation and excitatory/inhibitory balance that could serve as potential targets for therapeutics and diagnostic biomarkers. In addition, the regional differences in brain inflammation and synaptic protein expression indicate an epileptogenic zone from where the generalized seizures in synapsin 2 knockout mice may be initiated or spread. PMID:26177381
Diffuse alterations in synaptic protein expression following focal traumatic brain injury in the immature rat
G. T. Gobbel; C. Bonfield; E. B. Carson-Walter; P. D. Adelson
Introduction The mechanisms responsible for cognitive decline after traumatic brain injury (TBI) in pediatric patients are poorly understood.\\u000a The present study examined the potential role of synaptic alterations in this process by using an animal model of immature\\u000a head injury to define the impact of TBI on expression of the synaptic protein, synaptophysin.\\u000a \\u000a \\u000a \\u000a Materials and methods After craniotomy, TBI was induced in
Gene expression alterations in brains of mice infected with three strains of scrapie
Skinner, Pamela J; Abbassi, Hayet; Chesebro, Bruce; Race, Richard E; Reilly, Cavan; Haase, Ashley T
Background Transmissible spongiform encephalopathies (TSEs) or prion diseases are fatal neurodegenerative disorders which occur in humans and various animal species. Examples include Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in deer and elk, and scrapie in sheep, and experimental mice. To gain insights into TSE pathogenesis, we made and used cDNA microarrays to identify disease-associated alterations in gene expression. Brain gene expression in scrapie-infected mice was compared to mock-infected mice at pre-symptomatic and symptomatic time points. Three strains of mouse scrapie that show striking differences in neuropathology were studied: ME7, 22L, and Chandler/RML. Results In symptomatic mice, over 400 significant gene expression alterations were identified. In contrast, only 22 genes showed significant alteration in the pre-symptomatic animals. We also identified genes that showed significant differences in alterations in gene expression between strains. Genes identified in this study encode proteins that are involved in many cellular processes including protein folding, endosome/lysosome function, immunity, synapse function, metal ion binding, calcium regulation and cytoskeletal function. Conclusion These studies shed light on the complex molecular events that occur during prion disease, and identify genes whose further study may yield new insights into strain specific neuropathogenesis and ante-mortem tests for TSEs. PMID:16700923
Spread of epileptic activity in human brain
NASA Astrophysics Data System (ADS)
Milton, John
For many patients with medically refractory epilepsy surgical resection of the site of seizure onset (epileptic focus) offers the best hope for cure. Determination of the nature of seizure propagation should lead to improved methods for locating the epileptic focus (and hence reduce patient morbidity) and possibly to new treatment modalities directed at blocking seizure spread. Theoretical studies of neural networks emphasize the role of traveling waves for the propagation of activity. However, the nature of seizure propagation in human brain remains poorly characterized. The spread of epileptic activity in patients undergoing presurgical evaluation for epilepsy surgery was measured by placing subdural grids of electrodes (interelectrode spacings of 3-10 mm) over the frontal and temporal lobes. The exact location of each electrode relative to the surface of the brain was determined using 3--D MRI imaging techniques. Thus it is possible to monitor the spread of epileptic activity in both space and time. The observations are discussed in light of models for seizure propagation.
Altering the Brain Circuits for Reading Through Intervention: A Magnetic Source Imaging Study
Panagiotis G. Simos; Jack M. Fletcher; Shirin Sarkari; Rebecca L. Billingsley; Carolyn Denton; Andrew C. Papanicolaou
Intervention-related changes in spatiotemporal profiles of regional brain activation were examined by whole-head magnetoencephalography in 15 children with severe reading difficulties who had failed to show adequate progress to quality reading instruction during Grade 1. Intensive intervention initially focused on phonological decoding skills (for 8 weeks) and, during the subsequent 8 weeks, on rapid word recognition ability. Clinically significant improvement
Rapamycin ameliorates brain metabolites alterations after transient focal ischemia in rats.
Chauhan, Anjali; Sharma, Uma; Jagannathan, Naranamangalam R; Gupta, Yogendra Kumar
Rapamycin has been shown to protect against middle cerebral artery occlusion (MCAo) induced ischemic injury. In this study, the neuroprotective effect of rapamycin on the metabolic changes induced by MCAo was evaluated using nuclear magnetic resonance (NMR) spectroscopy of brain tissues. MCAo in rats was induced by insertion of nylon filament. One hour after ischemia, rapamycin (250µg/kg, i.p.) in dimethyl sulfoxide was administered. Reperfusion was done 2h after ischemia. Twenty-four hours after ischemia phospholipase A2 (PLA2) levels and metabolic changes were assessed. Perchloric acid extraction was performed on the brain of all animals (n=7; sham, vehicle; DMSO and rapamycin 250µg/kg) and the various brain metabolites were assessed by NMR spectroscopy. In all 44 metabolites were assigned in the proton NMR spectrum of rat brain tissues. In the vehicle group, we observed increased lactate levels and decreased levels of glutamate/glutamine, choline containing compounds, creatine/phosphocreatine (Cr/PCr), taurine, myo-inositol, ?-amino butryic acid (GABA), N-aspartyl aspartate (NAA), purine and pyrimidine metabolites. In rapamycin treated rats, there was increase in the levels of choline containing compounds, NAA, myo-inositol, glutamate/glutamine, GABA, Cr/PCr and taurine as compared to those of vehicle control (P<0.05). Rapamycin treatment reduced PLA2 levels as compared to vehicle group (P<0.05). Our findings indicated that rapamycin reduced the increased PLA2 levels and altered brain metabolites after MCAo. These protective effects might be attributed to its effect on cell membrane metabolism; glutamate induced toxicity and calcium homeostasis in stroke. PMID:25814258
Activation of calcineurin underlies altered trafficking of ?2 subunit containing GABAA receptors during prolonged epileptiform activity
Eckel, Ramona; Szulc, Blanka; Walker, Matthew C.; Kittler, Josef T.
Fast inhibitory signalling in the mammalian brain is mediated by gamma-aminobutyric acid type A receptors (GABAARs), which are targets for anti-epileptic therapy such as benzodiazepines. GABAARs undergo tightly regulated trafficking processes that are essential for maintenance and physiological modulation of inhibitory strength. The trafficking of GABAARs to and from the membrane is altered during prolonged seizures such as in Status Epilepticus (SE) and has been suggested to contribute to benzodiazepine pharmacoresistance in patients with SE. However, the intracellular signalling mechanisms that cause this modification in GABAAR trafficking remain poorly understood. In this study, we investigate the surface stability of GABAARs during SE utilising the low Mg2+ model in hippocampal rat neurons. Live-cell imaging of super ecliptic pHluorin (SEP)-tagged ?2 subunit containing GABAARs during low Mg2+ conditions reveals that the somatic surface receptor pool undergoes down-regulation dependent on N-methyl-d-aspartate receptor (NMDAR) activity. Analysis of the intracellular Ca2+ signal during low Mg2+ using the Ca2+-indicator Fluo4 shows that this reduction of surface GABAARs correlates well with the timeline of intracellular Ca2+ changes. Furthermore, we show that the activation of the phosphatase calcineurin was required for the decrease in surface GABAARs in neurons undergoing epileptiform activity. These results indicate that somatic modulation of GABAAR trafficking during epileptiform activity in vitro is mediated by calcineurin activation which is linked to changes in intracellular Ca2+ concentrations. These mechanisms could account for benzodiazepine pharmacoresistance and the maintenance of recurrent seizure activity, and reveal potential novel targets for the treatment of SE. This article is part of the Special Issue entitled 'GABAergic Signaling in Health and Disease'. PMID:25245802
NeuroimagingDecoding mental states from brain activity in humans
Geraint Rees; John-Dylan Haynes
Recent advances in human neuroimaging have shown that it is possible to accurately decode a person's conscious experience based only on non-invasive measurements of their brain activity. Such 'brain reading' has mostly been studied in the domain of visual perception, where it helps reveal the way in which individual experiences are encoded in the human brain. The same approach can
Order/disorder in brain electrical activity
NASA Astrophysics Data System (ADS)
Rosso, O. A.; Figliola, Y. A.
The processing of information by the brain is reflected in dynamical changes of the electrical activity in time, frequency, and space. Therefore, the concomitant studies require methods capable of describing the quantitative variation of the signal in both time and frequency. Here we present a quantitative EEG (qEEG) analysis, based on the Orthogonal Discrete Wavelet Transform (ODWT), of generalized epileptic tonic-clonic EEG signals. Two quantifiers: the Relative Wavelet Energy (RWE) and the Normalized Total Wavelet Entropy (NTWS) have been used. The RWE gives information about the relative energy associated with the different frequency bands present in the EEG and their corresponding degree of importance. The NTWS is a measure of the order/disorder degree in the EEG signal. These two quantifiers were computing in EEG signals as provided by scalp electrodes of epileptic patients. We showed that the epileptic recruitment rhythm observed for generalized epileptic tonic-clonic seizures is accurately described by the RWE quantifier. In addition, a significant decrease in the NTWS was observed in the recruitment epoch, indicating a more rhythmic and ordered behavior in the brain electrical activity.
Brain Activity with Reading Sentences and Emoticons
NASA Astrophysics Data System (ADS)
Yuasa, Masahide; Saito, Keiichi; Mukawa, Naoki
In this paper, we describe a person's brain activity when he/she sees an emoticon at the end of a sentence. An emoticon consists of some characters that resemble the human face and expresses a sender's emotion. With the help of a computer network, we use e-mail, messenger, avatars and so on, in order to convey what we wish to, to a receiver. Moreover, we send an emotional expression by using an emoticon at the end of a sentence. In this research, we investigate the effect of an emoticon as nonverbal information, using an fMRI study. The experimental results show that the right and left inferior frontal gyrus were activated and we detect a sentence with an emoticon as the verbal and nonverval information.
Altered brain morphometry in carpal tunnel syndrome is associated with median nerve pathology???
Maeda, Yumi; Kettner, Norman; Sheehan, James; Kim, Jieun; Cina, Stephen; Malatesta, Cristina; Gerber, Jessica; McManus, Claire; Mezzacappa, Pia; Morse, Leslie R.; Audette, Joseph; Napadow, Vitaly
Objective Carpal tunnel syndrome (CTS) is a common median nerve entrapment neuropathy characterized by pain, paresthesias, diminished peripheral nerve conduction velocity (NCV) and maladaptive functional brain neuroplasticity. We evaluated structural reorganization in brain gray matter (GM) and white matter (WM) and whether such plasticity is linked to altered median nerve function in CTS. Methods We performed NCV testing, T1-weighted structural MRI, and diffusion tensor imaging (DTI) in 28 CTS and 28 age-matched healthy controls (HC). Voxel-based morphometry (VBM) contrasted regional GM volume for CTS versus HC. Significant clusters were correlated with clinical metrics and served as seeds to define associated WM tracts using DTI data and probabilistic tractography. Within these WM tracts, fractional anisotropy (FA), axial (AD) and radial (RD) diffusivity were evaluated for group differences and correlations with clinical metrics. Results For CTS subjects, GM volume was significantly reduced in contralesional S1 (hand-area), pulvinar and frontal pole. GM volume in contralesional S1 correlated with median NCV. NCV was also correlated with RD and was negatively correlated with FA within U-fiber cortico-cortical association tracts identified from the contralesional S1 VBM seed. Conclusions Our study identified clear morphometric changes in the CTS brain. This central morphometric change is likely secondary to peripheral nerve pathology and altered somatosensory afference. Enhanced axonal coherence and myelination within cortico-cortical tracts connecting primary somatosensory and motor areas may accompany peripheral nerve deafferentation. As structural plasticity was correlated with NCV and not symptomatology, the former may be a better determinant of appropriate clinical intervention for CTS, including surgery. PMID:23799199
Brain Alterations and Clinical Symptoms of Dementia in Diabetes: A?/Tau-Dependent and Independent Mechanisms
Sato, Naoyuki; Morishita, Ryuichi
Emerging evidence suggests that diabetes affects cognitive function and increases the incidence of dementia. However, the mechanisms by which diabetes modifies cognitive function still remains unclear. Morphologically, diabetes is associated with neuronal loss in the frontal and temporal lobes including the hippocampus, and aberrant functional connectivity of the posterior cingulate cortex and medial frontal/temporal gyrus. Clinically, diabetic patients show decreased executive function, information processing, planning, visuospatial construction, and visual memory. Therefore, in comparison with the characteristics of AD brain structure and cognition, diabetes seems to affect cognitive function through not only simple AD pathological feature-dependent mechanisms but also independent mechanisms. As an A?/tau-independent mechanism, diabetes compromises cerebrovascular function, increases subcortical infarction, and might alter the blood–brain barrier. Diabetes also affects glucose metabolism, insulin signaling, and mitochondrial function in the brain. Diabetes also modifies metabolism of A? and tau and causes A?/tau-dependent pathological changes. Moreover, there is evidence that suggests an interaction between A?/tau-dependent and independent mechanisms. Therefore, diabetes modifies cognitive function through A?/tau-dependent and independent mechanisms. Interaction between these two mechanisms forms a vicious cycle. PMID:25250014
Structural alterations of the social brain: a comparison between schizophrenia and autism.
Radeloff, Daniel; Ciaramidaro, Angela; Siniatchkin, Michael; Hainz, Daniela; Schlitt, Sabine; Weber, Bernhard; Poustka, Fritz; Bölte, Sven; Walter, Henrik; Freitag, Christine Margarete
Autism spectrum disorder and schizophrenia share a substantial number of etiologic and phenotypic characteristics. Still, no direct comparison of both disorders has been performed to identify differences and commonalities in brain structure. In this voxel based morphometry study, 34 patients with autism spectrum disorder, 21 patients with schizophrenia and 26 typically developed control subjects were included to identify global and regional brain volume alterations. No global gray matter or white matter differences were found between groups. In regional data, patients with autism spectrum disorder compared to typically developed control subjects showed smaller gray matter volume in the amygdala, insula, and anterior medial prefrontal cortex. Compared to patients with schizophrenia, patients with autism spectrum disorder displayed smaller gray matter volume in the left insula. Disorder specific positive correlations were found between mentalizing ability and left amygdala volume in autism spectrum disorder, and hallucinatory behavior and insula volume in schizophrenia. Results suggest the involvement of social brain areas in both disorders. Further studies are needed to replicate these findings and to quantify the amount of distinct and overlapping neural correlates in autism spectrum disorder and schizophrenia. PMID:25188200
A new stress model, a scream sound, alters learning and monoamine levels in rat brain.
Hu, Lili; Yang, Juan; Song, Tusheng; Hou, Ni; Liu, Yong; Zhao, Xiaoge; Zhang, Dianzeng; Wang, Lumin; Wang, Tao; Huang, Chen
Most existing animal models for stress involve the simultaneous application of physical and psychological stress factors. In the current study, we described and used a novel psychological stress model (scream sound stress). To study the validity of it, we carried out acute and chronic scream sound stress. First, adult Sprague-Dawley (SD) rats were randomly divided into white noise, stress and background groups. The white noise group and stress group were treated with white noise and scream sound for 4h in the morning respectively. Compared with white noise and background groups, exposure to acute scream sound increased corticosterone (CORT) level and decreased latency in Morris water maze (MWM) test. The levels of noradrenaline (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were altered in the striatum, hypothalamus and hippocampus of stress rats. Second, adult SD rats were randomly divided into background and stress groups, which were treated with scream sound for three weeks. Exposure to chronic scream sound suppressed body weight gain, increased corticosterone (CORT) level, influenced the morphology of adrenal gland, improved spleen and thymus indices, and decreased latency in MWM test. NE, DA, DOPAC, HVA and 5-HIAA levels were also altered in the brain of stress rats. Our results suggested that scream sound, as a novel stressor, facilitated learning ability, as well as altered monoamine levels in the rat brain. Moreover, scream sound is easy to apply and can be applied in more animals at the same time. PMID:24096192
Chronology and chronicity of altered resting-state functional connectivity after traumatic brain injury.
Venkatesan, Umesh M; Dennis, Nancy A; Hillary, Frank G
Whereas traumatic brain injury (TBI) results in widespread disruption of neural networks, changes in regional resting-state functional connectivity patterns after insult remain unclear. Specifically, little is known about the chronology of emergent connectivity alterations and whether they persist after a critical recovery window. We used resting-state functional magnetic resonance imaging and seed-voxel correlational analyses in both cross-sectional and longitudinal designs to probe intrinsic connectivity patterns involving the posterior cingulate cortex (PCC) and hippocampi, regions shown to be important in the default mode network (DMN) and vulnerable to neuropathology. A total of 22 participants in the chronic stage of moderate-to-severe TBI and 18 healthy controls were included for cross-sectional study. Longitudinal analyses included 13 individuals in the TBI group for whom data approximately 3 months after injury (subacute) were available. Overall, results indicated dissociable connectivity trajectories of the PCC and hippocampi during recovery from TBI, with PCC alterations characterized by early hypersynchrony with the anterior DMN that is gradually reduced, and hippocampal changes marked by increasing synchrony with proximal cortex and subcortex. The PCC also showed increasing antiphase synchrony with posterior attentional regions, and the hippocampi showed decreasing antiphase synchrony with frontal attentional regions. Antiphase synchrony of the hippocampus and dorsolateral prefrontal cortex at the subacute stage of TBI was positively associated with attentional performance on neuropsychological tests at both the subacute and chronic stages. Our findings highlight the heterogeneity of regional whole-brain connectivity changes after TBI, and suggest that residual connectivity alterations exist in the clinically stable phase of TBI. Parallels between the chronicity of the observed effects and findings in neurodegenerative disease are discussed in the context of potential long-term outcomes of TBI. PMID:24955788
Maternal Pravastatin Prevents Altered Fetal Brain Development in a Preeclamptic CD-1 Mouse Model
Carver, Alissa R.; Andrikopoulou, Maria; Lei, Jun; Tamayo, Esther; Gamble, Phyllis; Hou, Zhipeng; Zhang, Jiangyang; Mori, Susumu; Saade, George R.; Costantine, Maged M.; Burd, Irina
Objective Using an animal model, we have previously shown that preeclampsia results in long-term adverse neuromotor outcomes in the offspring, and this phenotype was prevented by antenatal treatment with pravastatin. This study aims to localize the altered neuromotor programming in this animal model and to evaluate the role of pravastatin in its prevention. Materials and Methods For the preeclampsia model, pregnant CD-1 mice were randomly allocated to injection of adenovirus carrying sFlt-1 or its control virus carrying mFc into the tail vein. Thereafter they received pravastatin (sFlt-1-pra "experimental group") or water (sFlt-1 "positive control") until weaning. The mFc group ("negative control") received water. Offspring at 6 months of age were sacrificed, and whole brains underwent magnetic resonance imaging (MRI). MRIs were performed using an 11.7 Tesla vertical bore MRI scanner. T2 weighted images were acquired to evaluate the volumes of 28 regions of interest, including areas involved in adaptation and motor, spatial and sensory function. Cytochemistry and cell quantification was performed using neuron-specific Nissl stain. One-way ANOVA with multiple comparison testing was used for statistical analysis. Results Compared with control offspring, male sFlt-1 offspring have decreased volumes in the fimbria, periaquaductal gray, stria medullaris, and ventricles and increased volumes in the lateral globus pallidus and neocortex; however, female sFlt-1 offspring showed increased volumes in the ventricles, stria medullaris, and fasciculus retroflexus and decreased volumes in the inferior colliculus, thalamus, and lateral globus pallidus. Neuronal quantification via Nissl staining exhibited decreased cell counts in sFlt-1 offspring neocortex, more pronounced in males. Prenatal pravastatin treatment prevented these changes. Conclusion Preeclampsia alters brain development in sex-specific patterns, and prenatal pravastatin therapy prevents altered neuroanatomic programming in this animal model. PMID:24963809
Brain alteration in a Nude/SCID fetus carrying FOXN1 homozygous mutation.
Amorosi, Stefania; Vigliano, Ilaria; Del Giudice, Ennio; Panico, Luigi; Maruotti, Giuseppe M; Fusco, Anna; Quarantelli, Mario; Ciccone, Carla; Ursini, Matilde V; Martinelli, Pasquale; Pignata, Claudio
A critical role of the FOX transcription factors in the development of different tissues has been shown. Among these genes, FOXN1 encodes a protein whose alteration is responsible for the Nude/SCID phenotype. Recently, our group reported on a human Nude/SCID fetus, which also had severe neural tube defects, namely anencephaly and spina bifida. This led to hypothesize that FOXN1 could have a role in the early stages of central nervous system development. Here we report on a second fetus that carried the R255X homozygous mutation in FOXN1 that has been examined for the presence of CNS developmental anomalies. At 16 postmenstrual weeks of gestation, the abdominal ultrasonography of the Nude/SCID fetus revealed a morphologically normal brain, but with absence of cavum septi pellucidi (CSP). Moreover, after confirmation of the diagnosis of severe Nude/SCID, the fetus was further examined postmortem and a first gross examination revealed an enlargement of the interhemispheric fissure. Subsequently, a magnetic resonance imaging failed to identify the corpus callosum in any section. In conclusion, our observations did not reveal any gross abnormalities in the CNS anatomy of the Nude/SCID fetus, but alteration of the corpus callosum, suggesting that FOXN1 alterations could play a role as a cofactor in CNS development in a similar fashion to other FOX family members. PMID:20864124
Diffuse axonal injury in brain trauma: insights from alterations in neurofilaments
Siedler, Declan G.; Chuah, Meng Inn; Kirkcaldie, Matthew T. K.; Vickers, James C.; King, Anna E.
Traumatic brain injury (TBI) from penetrating or closed forces to the cranium can result in a range of forms of neural damage, which culminate in mortality or impart mild to significant neurological disability. In this regard, diffuse axonal injury (DAI) is a major neuronal pathophenotype of TBI and is associated with a complex set of cytoskeletal changes. The neurofilament triplet proteins are key structural cytoskeletal elements, which may also be important contributors to the tensile strength of axons. This has significant implications with respect to how axons may respond to TBI. It is not known, however, whether neurofilament compaction and the cytoskeletal changes that evolve following axonal injury represent a component of a protective mechanism following damage, or whether they serve to augment degeneration and progression to secondary axotomy. Here we review the structure and role of neurofilament proteins in normal neuronal function. We also discuss the processes that characterize DAI and the resultant alterations in neurofilaments, highlighting potential clues to a possible protective or degenerative influence of specific neurofilament alterations within injured neurons. The potential utility of neurofilament assays as biomarkers for axonal injury is also discussed. Insights into the complex alterations in neurofilaments will contribute to future efforts in developing therapeutic strategies to prevent, ameliorate or reverse neuronal degeneration in the central nervous system (CNS) following traumatic injury. PMID:25565963
Alzheimer's disease and type 2 diabetes-related alterations in brain mitochondria, autophagy and synaptic markers.
Carvalho, Cristina; Santos, Maria S; Oliveira, Catarina R; Moreira, Paula I
We aimed to investigate mitochondrial function, biogenesis and autophagy in the brain of type 2 diabetes (T2D) and Alzheimer's disease (AD) mice. Isolated brain mitochondria and homogenates from cerebral cortex and hippocampus of wild-type (WT), triple transgenic AD (3xTg-AD) and T2D mice were used to evaluate mitochondrial functional parameters and protein levels of mitochondrial biogenesis, autophagy and synaptic integrity markers, respectively. A significant decrease in mitochondrial respiration, membrane potential and energy levels was observed in T2D and 3xTg-AD mice. Also, a significant decrease in the levels of autophagy-related protein 7 (ATG7) and glycosylated lysosomal membrane protein 1 (LAMP1) was observed in cerebral cortex and hippocampus of T2D and 3xTg-AD mice. Moreover, both brain regions of 3xTg-AD mice present lower levels of nuclear respiratory factor (NRF) 1 while the levels of NRF2 are lower in both brain regions of T2D and 3xTg-AD mice. A decrease in mitochondrial encoded, nicotinamide adenine dinucleotide dehydrogenase subunit 1 (ND1) was also observed in T2D and 3xTg-AD mice although only statistically significant in T2D cortex. Furthermore, a decrease in the levels of postsynaptic density protein 95 (PSD95) in the cerebral cortex of 3xTg-AD mice and in hippocampus of T2D and 3xTg-AD mice and a decrease in the levels of synaptosomal-associated protein 25 (SNAP 25) in the hippocampus of T2D and 3xTg-AD mice were observed suggesting synaptic integrity loss. These results support the idea that alterations in mitochondrial function, biogenesis and autophagy cause synaptic damage in AD and T2D. PMID:25960150
Methamphetamine Alters Blood Brain Barrier Protein Expression in Mice, Facilitating Central Nervous System Infection by Neurotropic Cryptococcus neoformans
Eugenin, Eliseo A.; Greco, Jade M.; Frases, Susana; Nosanchuk, Joshua D.; Martinez, Luis R.
Methamphetamine (METH) is a drug of abuse that is a potent and highly addictive central nervous system (CNS) stimulant. The blood brain barrier (BBB) is a unique interface that in part functions to prevent microbial invasion of the CNS. The effects of METH on brain vasculature have not been studied extensively. We hypothesized that METH alters the BBB integrity, increasing susceptibility to CNS infection. Using a murine model of METH administration, we demonstrated that METH alters BBB integrity and modifies the expression of tight junction and adhesion molecules. Additionally, we showed that BBB disruption accelerates transmigration of the neurotropic fungus Cryptococcus neoformans into the brain parenchyma after systemic infection. Furthermore, METH-treated mice displayed increased mortality as compared to untreated animals. Our findings provide novel evidence of the impact of METH abuse on the integrity of the cells that comprise the BBB and protect the brain from infection. PMID:23532099
Methamphetamine alters blood brain barrier protein expression in mice, facilitating central nervous system infection by neurotropic Cryptococcus neoformans.
Eugenin, Eliseo A; Greco, Jade M; Frases, Susana; Nosanchuk, Joshua D; Martinez, Luis R
Methamphetamine (METH) is a drug of abuse that is a potent and highly addictive central nervous system (CNS) stimulant. The blood brain barrier (BBB) is a unique interface that in part functions to prevent microbial invasion of the CNS. The effects of METH on brain vasculature have not been studied extensively. We hypothesized that METH alters the BBB integrity, increasing susceptibility to CNS infection. Using a murine model of METH administration, we demonstrated that METH alters BBB integrity and modifies the expression of tight junction and adhesion molecules. Additionally, we showed that BBB disruption accelerates transmigration of the neurotropic fungus Cryptococcus neoformans into the brain parenchyma after systemic infection. Furthermore, METH-treated mice displayed increased mortality as compared to untreated animals. Our findings provide novel evidence of the impact of METH abuse on the integrity of the cells that comprise the BBB and protect the brain from infection. PMID:23532099
Alterations in function and expression of ABC transporters at blood-brain barrier under diabetes and the clinical significances
Liu, Li; Liu, Xiao-Dong
Diabetes is a systematic metabolic disease, which often develops a number of well-recognized vascular complications including brain complications which may partly result from the dysfunction of blood-brain barrier (BBB). BBB is generally considered as a mechanism for protecting the brain from unwanted actions resulting from substances in the blood and maintaining brain homeostasis via monitoring the entry or efflux of compounds. ATP-binding cassette (ABC) family of transporters including P-glycoprotein (P-GP) and breast cancer-related protein (BCRP), widely expressed in the luminal membrane of the microvessel endothelium and in the apical membrane of the choroids plexus epithelium, play important roles in the function of BBB. However, these transporters are easily altered by some diseases. The present article was focused on the alteration in expression and function of both P-GP and BCRP at BBB by diabetes and the clinical significances. PMID:25540622
Determinants of brain activation-induced cortical NAD/NADH responses in vivo.
Dóra, E; Gyulai, L; Kovách, A G
In order to elucidate that which are the factors that may influence the direction of brain activation-induced changes in the redox state of oxidized/reduced nicotinamide adenine dinucleotide (NAD/NADH), the brain cortex was electrically stimulated during arterial hypotension and following reinfusion of the shed blood, during arterial hyper- and hypoxia, and during the second phase of spreading cortical depression (SD). Cerebrocortical NADH fluorescence and vascular volume ( CVV ) of cats, anaesthetized by chloralose, were measured with a microscope fluororeflectometer . Under physiologically normal conditions electrical stimulation resulted in pronounced cortical NAD reduction and increase in CVV . These reactions were not altered by arterial hyperoxia and continuous superfusion of the brain cortex with oxygenated artificial cerebrospinal fluid (mock CSF). Arterial hypotension and SD (in phase II) increased NAD reduction and CVV markedly, and the superimposed electrical stimulation brought about NADH oxidation and greatly depressed CVV responses. Reinfusion of the shed blood did not restore NAD/NADH redox state and CVV to their reference levels, and electrical stimulation under this condition led to NADH oxidation and negligible vascular reactions. Since under physiologically normal conditions electrical activation of the brain cortex resulted in NAD reduction and marked increase in CVV and the magnitude of these reactions were not altered by arterial hyperoxia or by superfusion of the brain cortex with oxygenated CSF, it is very unlikely that the brain cortex became hypoxic during stimulation. Because when the steady NAD/NADH redox state of the brain cortex was shifted toward reduction by arterial hypotension and reinfusion and SD, electrical stimulation led to NADH oxidation, it is suggested that the prestimulatory steady redox state has great importance in determining the direction of NAD/NADH redox reactions evoked by activation of the brain cortex. PMID:6326966
Cellular proliferation and infiltration following interstitial irradiation of normal dog brain is altered by an inhibitor of polyamine synthesis
Fike, J.R.; Gobbel, G.T.; Chou, D. [Univ. of California, San Francisco, CA (United States)] [and others] [Univ. of California, San Francisco, CA (United States); and others
The objectives of this study were to quantitatively define proliferative and infiltrative cell responses after focal {sup 125}I irradiation of normal brain, and to determine the effects of an intravenous infusion of {alpha}-defluoromethylornithine (DFMO) on those responses. Adult beagle dogs were irradiated using high activity {sup 125}I sources. Cellular responses were quantified using a histomorphometric analysis. After radiation alone, cellular events included a substantial acute inflammatory response followed by increased BrdU labeling and progressive increases in numbers of capillaries and astrocytes. {alpha}-Difluoromethylornithine treatment significantly affected the measured cell responses. As in controls, an early inflammatory response was measured, but after 2 weeks there were more PMNs/unit area than in controls. The onset of measurable BrdU labeling was delayed in DFMO-treated animals, and the magnitude of labeling was significantly reduced. Increases in astrocyte and vessel numbers/mm{sup 2} were observed after a 2-week delay. At the site of implant, astrocytes from DFMO-treated dogs were significantly smaller than those from controls. There is substantial cell proliferation and infiltration in response to interstitial irradiation of normal brain, and these responses are significantly altered by DFMO treatment. Although the precise mechanisms by which DFMO exerts its effects in this model are not known, the results from this study suggest that modification of radiation injury may be possible by manipulating the response of normal cells to injury. 57 refs., 6 figs.
Effect of hypothermia on bilirubin-induced alterations in brain cell membrane function and energy metabolism in newborn piglets
Won Soon Park; Yun Sil Chang; So Hee Chung; Dae Won Seo; Sung Hwa Hong; Munhyang Lee
The aim of this study was to evaluate the effects of hypothermia on bilirubin-induced alterations in brain cell membrane function and energy metabolism in the developing brain. Thirty-seven newborn piglets were divided randomly into four groups: normothermic control (NC, n=9); hypothermic control (HC, n=7); normothermic bilirubin infusion (NB, n=11); and hypothermic bilirubin infusion (HB, n=10) groups. In bilirubin infusion groups
Detection of pathological molecular alterations in scrapie-infected hamster brain by Fourier transform infrared (FT-IR) spectroscopy
Janina Kneipp; Peter Lasch; Elizabeth Baldauf; Michael Beekes; Dieter Naumann
In this report a new approach for the identification of pathological changes in scrapie-infected Syrian hamster brains using Fourier transform infrared microspectroscopy is discussed. Using computer-based pattern recognition techniques and imaging, infrared maps with high structural contrast were obtained. This strategy permitted comparison of spectroscopic data from identical anatomical structures in scrapie-infected and control brains. Consistent alterations in membrane state-of-order,
On a Quantum Model of Brain Activities
NASA Astrophysics Data System (ADS)
Fichtner, K.-H.; Fichtner, L.; Freudenberg, W.; Ohya, M.
One of the main activities of the brain is the recognition of signals. A first attempt to explain the process of recognition in terms of quantum statistics was given in [6]. Subsequently, details of the mathematical model were presented in a (still incomplete) series of papers (cf. [7, 2, 5, 10]). In the present note we want to give a general view of the principal ideas of this approach. We will introduce the basic spaces and justify the choice of spaces and operations. Further, we bring the model face to face with basic postulates any statistical model of the recognition process should fulfill. These postulates are in accordance with the opinion widely accepted in psychology and neurology.
Alterations in free radical scavenger system profile of type I diabetic rat brain
Sanjeev Kumar Bhardwaj; Poonam Sharma; Gurcharan Kaur
The activities of the enzymes related to glutathione synthesis, degradation, and functions as well as reactive oxygen scavenging\\u000a enzymes were analyzed in different brain regions, such as cerebral hemisphere, cerebellum, brainstem, thalamus, and hypothalamus\\u000a after 1 and 3 mo of streptozotocin-induced diabetes in rats. Parallel studies were also made in age-matched control rats and\\u000a insulin-treated diabetic rats. The content of
Binding sites for atrial natriuretic factor (ANF) in brain: alterations in Brattleboro rats
McCarty, R.; Plunkett, L.M.
Binding sites for atrial natriuretic factor (ANF-28) were analyzed in discrete brain areas of Brattleboro rats with hereditary diabetes insipidus and Long-Evans (LE) controls by quantitative autoradiography. The maximum binding capacity (Bmax) and affinity constant (Ka) for /sup 125/I-ANF-28 were elevated significantly in the subfornical organ of Brattleboro rats compared to matched LE controls. In contrast, values for Bmax and Ka for /sup 125/I-ANF-28 binding in choroid plexus and area postrema were similar for rats of the two strains. These findings are consistent with a selective upregulation of ANF-28 binding sites in the subfornical organ of Brattleboro rats which exhibit a profound disturbance in body fluid homeostasis. These alterations in ANF-28 binding sites in the subfornical organ may represent a compensatory response to the absence of vasopressin in the Brattleboro rat.
Artifact suppression and analysis of brain activities with electroencephalography signals
Rashed-Al-Mahfuz, Md.; Islam, Md. Rabiul; Hirose, Keikichi; Molla, Md. Khademul Islam
Brain-computer interface is a communication system that connects the brain with computer (or other devices) but is not dependent on the normal output of the brain (i.e., peripheral nerve and muscle). Electro-oculogram is a dominant artifact which has a significant negative influence on further analysis of real electroencephalography data. This paper presented a data adaptive technique for artifact suppression and brain wave extraction from electroencephalography signals to detect regional brain activities. Empirical mode decomposition based adaptive thresholding approach was employed here to suppress the electro-oculogram artifact. Fractional Gaussian noise was used to determine the threshold level derived from the analysis data without any training. The purified electroencephalography signal was composed of the brain waves also called rhythmic components which represent the brain activities. The rhythmic components were extracted from each electroencephalography channel using adaptive wiener filter with the original scale. The regional brain activities were mapped on the basis of the spatial distribution of rhythmic components, and the results showed that different regions of the brain are activated in response to different stimuli. This research analyzed the activities of a single rhythmic component, alpha with respect to different motor imaginations. The experimental results showed that the proposed method is very efficient in artifact suppression and identifying individual motor imagery based on the activities of alpha component. PMID:25206446
Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain
Prasunpriya Nayak; Ajay K Chatterjee
BACKGROUND: Alteration of glutamate and ?-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and ?-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter
Lack of cyclin D2 impairing adult brain neurogenesis alters hippocampal-dependent behavioral tasks without reducing learning ability.
Jedynak, Paulina; Jaholkowski, Piotr; Wozniak, Grazyna; Sandi, Carmen; Kaczmarek, Leszek; Filipkowski, Robert K
The exact function of the adult brain neurogenesis remains elusive, although it has been suggested to play a role in learning and memory processes. In our studies, we employed cyclin D2 gene knockout (cD2 KO) mice showing impaired neurogenesis as well as decreased hippocampal size. However, irrespectively of the genetic background of cD2 KO mice, this phenotype resulted in neither deficits in the hippocampal-dependent learning ability nor the memory formation. In the present study, cD2 KO mice and control littermates were subjected to hippocampal-dependent behavioral tests with little or no learning component. The knockout mice showed significant impairment in such species-typical behaviors as nest construction, digging, and marble burying. They were building none or poorer nests, digging less robustly, and burying fewer marbles than control mice. Such impairments were previously described, e.g., in animals with hippocampal lesions. Moreover, cD2 KO animals were also more active in the open field and automated motility chamber as well as showed increased explorative behavior in IntelliCage. Both increased motility and explorative behaviors were previously observed in hippocampally lesioned animals. Finally, cD2 KO mice showed normal sucrose preference, however starting from the second exposure to the sweetened solution, while control animals displayed a strong preference immediately. Presented results suggest that either morphological abnormalities of the hippocampal formation or adult brain neurogenesis impairment (or both) alter hippocampal-dependent behaviors of mutant mice without influencing learning abilities. These results may also suggest that adult brain neurogenesis is involved in species-typical behaviors. PMID:22101301
Potential moderators of physical activity on brain health.
Leckie, Regina L; Weinstein, Andrea M; Hodzic, Jennifer C; Erickson, Kirk I
Age-related cognitive decline is linked to numerous molecular, structural, and functional changes in the brain. However, physical activity is a promising method of reducing unfavorable age-related changes. Physical activity exerts its effects on the brain through many molecular pathways, some of which are regulated by genetic variants in humans. In this paper, we highlight genes including apolipoprotein E (APOE), brain derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT) along with dietary omega-3 fatty acid, docosahexaenoic acid (DHA), as potential moderators of the effect of physical activity on brain health. There are a growing number of studies indicating that physical activity might mitigate the genetic risks for disease and brain dysfunction and that the combination of greater amounts of DHA intake with physical activity might promote better brain function than either treatment alone. Understanding whether genes or other lifestyles moderate the effects of physical activity on neurocognitive health is necessary for delineating the pathways by which brain health can be enhanced and for grasping the individual variation in the effectiveness of physical activity interventions on the brain and cognition. There is a need for future research to continue to assess the factors that moderate the effects of physical activity on neurocognitive function. PMID:23304508
Potential Moderators of Physical Activity on Brain Health
Leckie, Regina L.; Weinstein, Andrea M.; Hodzic, Jennifer C.; Erickson, Kirk I.
Age-related cognitive decline is linked to numerous molecular, structural, and functional changes in the brain. However, physical activity is a promising method of reducing unfavorable age-related changes. Physical activity exerts its effects on the brain through many molecular pathways, some of which are regulated by genetic variants in humans. In this paper, we highlight genes including apolipoprotein E (APOE), brain derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT) along with dietary omega-3 fatty acid, docosahexaenoic acid (DHA), as potential moderators of the effect of physical activity on brain health. There are a growing number of studies indicating that physical activity might mitigate the genetic risks for disease and brain dysfunction and that the combination of greater amounts of DHA intake with physical activity might promote better brain function than either treatment alone. Understanding whether genes or other lifestyles moderate the effects of physical activity on neurocognitive health is necessary for delineating the pathways by which brain health can be enhanced and for grasping the individual variation in the effectiveness of physical activity interventions on the brain and cognition. There is a need for future research to continue to assess the factors that moderate the effects of physical activity on neurocognitive function. PMID:23304508
Vanadium improves brain acetylcholinesterase activity on early stage alloxan-diabetic rats.
Ghareeb, Doaa A; Hussen, Hend M
The present study is designed to screen the possible effects of sodium orthovanadate therapy on the kinetic parameters of brain membrane-bound and soluble acetylcholinesterase (AChE) forms in alloxan-induced diabetic rats. The diabetic rats were treated with 300 mg/kg sodium orthovanadate orally for 45 days. While diabetes significantly decreased the brain specific activity (V(max)) of AChE soluble form by 42%, it caused a fivefold increase of the K(m) of the membrane-bound form. Furthermore, the activity of brain glutathione-S-transferase (GST) was significantly decreased and this was associated with a remarkable increase in brain lipid peroxidative parameter, thiobarbituric acid reactive substances (TBARS), as compared to sham control. The alterations of both AChE forms observed in diabetic state could be attributed to hyperglycemia and lipid peroxidation that triggered brain dysfunction by disturbing the neurotransmitter acetylcholine level. Administration of sodium orthovanadate reversed the diabetic conditions by lowering the blood glucose level and normalized the blood Hb(A1C) level. It also normalized the levels of brain AChE, GST and TBARS as compared to diabetic state and control. Therefore, vanadate administration could protect against direct action of lipid peroxidation on brain AChE and in this way, it might be useful in the prevention of cholinergic neural dysfunction, which is one of the major complications in diabetes. PMID:18378083
Mouse Brain PSA-NCAM Levels Are Altered by Graded-Controlled Cortical Impact Injury
Budinich, Craig S.; Chen, HuaZhen; Lowe, Dennell; Rosenberger, John G.; Bernstock, Joshua D.; McCabe, Joseph T.
Traumatic brain injury (TBI) is a worldwide endemic that results in unacceptably high morbidity and mortality. Secondary injury processes following primary injury are composed of intricate interactions between assorted molecules that ultimately dictate the degree of longer-term neurological deficits. One comparatively unexplored molecule that may contribute to exacerbation of injury or enhancement of recovery is the posttranslationally modified polysialic acid form of neural cell adhesion molecule, PSA-NCAM. This molecule is a critical modulator of central nervous system plasticity and reorganization after injury. In this study, we used controlled cortical impact (CCI) to produce moderate or severe TBI in the mouse. Immunoblotting and immunohistochemical analysis were used to track the early (2, 24, and 48 hour) and late (1 and 3 week) time course and location of changes in the levels of PSA-NCAM after TBI. Variable and heterogeneous short- and long-term increases or decreases in expression were found. In general, alterations in PSA-NCAM levels were seen in the cerebral cortex immediately after injury, and these reductions persisted in brain regions distal to the primary injury site, especially after severe injury. This information provides a starting point to dissect the role of PSA-NCAM in TBI-related pathology and recovery. PMID:22848850
Rodent brain and heart catecholamine levels are altered by different models of copper deficiency
Pyatskowit, Joshua W.; Prohaska, Joseph R.
Limiting dopamine ?-monooxygenase results in lower norepinephrine (NE) and higher dopamine (DA) concentrations in copper-deficient (Cu?) tissues compared to copper-adequate (Cu+) tissues. Mice and rat offspring were compared to determine the effect of differences in dietary copper (Cu) deficiency started during gestation or lactation on catecholamine, NE and DA, content in brain and heart. Holtzman rat and Hsd:ICR (CD-1) outbred albino mouse dams were fed a Cu- diet and drank deionized water or Cu supplemented water. Offspring were sampled at time points between postnatal ages 12 and 27. For both rat and mouse Cu- tissue, NE and DA changes were greater at later ages. Though Cu restriction began earlier in rats than mice in the gestational model, brain NE reduction was more severe in Cu- mice than Cu- rats. Cardiac NE reduction was similar in Cu- rodents in the gestation models. In the lactation model, mouse catecholamines were altered more than rat catecholamines. Furthermore, following lactational Cu deficiency Cu- mice were anemic and exhibited cardiac hypertrophy, Cu- rats displayed neither phenotype. Within a species, changes were more severe and proportional to the length of Cu deprivation. Lactational Cu deficiency in mice had greater consequences than in rats. PMID:17287146
Altered phospholipid molecular species and glycolipid composition in brain, liver and fibroblasts of Zellweger syndrome.
Miyazaki, Celine; Saitoh, Makiko; Itoh, Masayuki; Yamashita, Sumimasa; Miyagishi, Makoto; Takashima, Sachio; Moser, Ann B; Iwamori, Masao; Mizuguchi, Masashi
We studied the altered molecular species of lipids in brain and liver tissues, and fibroblasts from patients with Zellweger syndrome (ZS). ZS cerebellum samples contained a higher amount of sphingomyelin with shorter chain fatty acids compared to that in normal controls. The amount of phosphatidylethanolamine (PE) was less than half of that in controls, with the absence of the PE-type of plasmalogen. Gangliosides were accumulated in the brains and fibroblasts of ZS patients. To investigate whether or not impaired beta-oxidation of very long chain fatty acids and/or plasmalogen synthesis affects glycolipids metabolism, RNAi of peroxisomal acylCo-A oxidase (ACOX1) and glyceronephosphate O-acyltransferase (GNPAT) was performed using cultured neural cells. In neuronal F3-Ngn1 cells, ACOX1 and GNPAT silencing up-regulated ceramide galactosyltransferase (UGT8) mRNA expression, and down-regulated UDP-glucose ceramide glucosyltransferase (UGCG). These results suggest that both impaired beta-oxidation of very long chain fatty acids and plasmalogen synthesis affect glycolipid metabolism in neuronal cells. PMID:23933200
Sustained NMDA receptor hypofunction induces compromised neural systems integration and schizophrenia-like alterations in functional brain networks.
Dawson, Neil; Xiao, Xiaolin; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A
Compromised functional integration between cerebral subsystems and dysfunctional brain network organization may underlie the neurocognitive deficits seen in psychiatric disorders. Applying topological measures from network science to brain imaging data allows the quantification of complex brain network connectivity. While this approach has recently been used to further elucidate the nature of brain dysfunction in schizophrenia, the value of applying this approach in preclinical models of psychiatric disease has not been recognized. For the first time, we apply both established and recently derived algorithms from network science (graph theory) to functional brain imaging data from rats treated subchronically with the N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP). We show that subchronic PCP treatment induces alterations in the global properties of functional brain networks akin to those reported in schizophrenia. Furthermore, we show that subchronic PCP treatment induces compromised functional integration between distributed neural systems, including between the prefrontal cortex and hippocampus, that have established roles in cognition through, in part, the promotion of thalamic dysconnectivity. We also show that subchronic PCP treatment promotes the functional disintegration of discrete cerebral subsystems and also alters the connectivity of neurotransmitter systems strongly implicated in schizophrenia. Therefore, we propose that sustained NMDA receptor hypofunction contributes to the pathophysiology of dysfunctional brain network organization in schizophrenia. PMID:23081884
Altered Brain Structure and Function Correlate with Disease Severity and Pain Catastrophizing in Migraine Patients
Hubbard, Catherine S.; Khan, Shariq A.; Keaser, Michael L.; Mathur, Vani A.; Goyal, Madhav; Seminowicz, David A.
To investigate the neuroanatomical and functional brain changes in migraine patients relative to healthy controls, we used a combined analytical approach including voxel- and surface-based morphometry along with resting-state functional connectivity to determine whether areas showing structural alterations in patients also showed abnormal functional connectivity. Additionally, we wanted to assess whether these structural and functional changes were associated with group differences in pain catastrophizing and migraine-related disease variables in patients. We acquired T1-weighted anatomical and functional magnetic resonance imaging scans during rest in human subjects with a diagnosis of migraine and healthy controls. Structural analyses revealed greater left hippocampal gray matter volume and reduced cortical thickness in the left anterior midcingulate in patients compared with controls. We also observed negative associations between pain catastrophizing and migraine disease variables and gray matter in areas implicated in processing the sensory, affective, and cognitive aspects of pain in patients. Functional connectivity analyses showed that migraine patients displayed disrupted connectivity between default mode, salience, cognitive, visuospatial, and sensorimotor networks, which was associated with group differences in pain catastrophizing and migraine-related disease variables in patients. Together, our findings show widespread morphological and functional brain abnormalities in migraineurs in affective, cognitive, visual, and pain-related brain areas, which are associated with increased pain catastrophizing, disease chronicity, and severity of symptoms, suggesting that these structural and functional changes may be a consequence of repeated, long-term nociceptive signaling leading to increased pain sensitivity, mood disturbances, and maladaptive coping strategies to deal with unrelenting pain. PMID:25893216
Altered brain phospholipid and acylcarnitine profiles in propionic acid infused rodents: further development of a potential model of autism spectrum disorders.
Thomas, Raymond H; Foley, Kelly A; Mepham, Jennifer R; Tichenoff, Lisa J; Possmayer, Fred; MacFabe, Derrick F
Recent studies have demonstrated intraventricular infusions of propionic acid (PPA) a dietary and enteric short-chain fatty acid can produce brain and behavioral changes similar to those observed in autism spectrum disorder (ASD). The effects of PPA were further evaluated to determine if there are any alterations in brain lipids associated with the ASD-like behavioral changes observed following intermittent intraventricular infusions of PPA, the related enteric metabolite butyric acid (BUT) or phosphate-buffered saline vehicle. Both PPA and BUT produced significant increases (p < 0.001) in locomotor activity (total distance travelled and stereotypy). PPA and to a lesser extent BUT infusions decreased the levels of total monounsaturates, total omega6 fatty acids, total phosphatidylethanolamine plasmalogens, the ratio of omega6 : omega3 and elevated the levels of total saturates in separated phospholipid species. In addition, total acylcarnitines, total longchain (C12-C24) acylcarnitines, total short-chain (C2 to C9) acylcarnitines, and the ratio of bound to free carnitine were increased following infusions with PPA and BUT. These results provide evidence of a relationship between changes in brain lipid profiles and the occurrence of ASD-like behaviors using the autism rodent model. We propose that altered brain fatty acid metabolism may contribute to ASD. PMID:20405543
Alterations in brain-derived neurotrophic factor in the mouse hippocampus following acute but not repeated benzodiazepine treatment.
Licata, Stephanie C; Shinday, Nina M; Huizenga, Megan N; Darnell, Shayna B; Sangrey, Gavin R; Rudolph, Uwe; Rowlett, James K; Sadri-Vakili, Ghazaleh
Benzodiazepines (BZs) are safe drugs for treating anxiety, sleep, and seizure disorders, but their use also results in unwanted effects including memory impairment, abuse, and dependence. The present study aimed to reveal the molecular mechanisms that may contribute to the effects of BZs in the hippocampus (HIP), an area involved in drug-related plasticity, by investigating the regulation of immediate early genes following BZ administration. Previous studies have demonstrated that both brain derived neurotrophic factor (BDNF) and c-Fos contribute to memory- and abuse-related processes that occur within the HIP, and their expression is altered in response to BZ exposure. In the current study, mice received acute or repeated administration of BZs and HIP tissue was analyzed for alterations in BDNF and c-Fos expression. Although no significant changes in BDNF or c-Fos were observed in response to twice-daily intraperitoneal (i.p.) injections of diazepam (10 mg/kg + 5 mg/kg) or zolpidem (ZP; 2.5 mg/kg + 2.5 mg/kg), acute i.p. administration of both triazolam (0.03 mg/kg) and ZP (1.0 mg/kg) decreased BDNF protein levels within the HIP relative to vehicle, without any effect on c-Fos. ZP specifically reduced exon IV-containing BDNF transcripts with a concomitant increase in the association of methyl-CpG binding protein 2 (MeCP2) with BDNF promoter IV, suggesting that MeCP2 activity at this promoter may represent a ZP-specific mechanism for reducing BDNF expression. ZP also increased the association of phosphorylated cAMP response element binding protein (pCREB) with BDNF promoter I. Future work should examine the interaction between ZP and DNA as the cause for altered gene expression in the HIP, given that BZs can enter the nucleus and intercalate into DNA directly. PMID:24367698
Monoaminergic neurotransmitter alterations in postmortem brain regions of depressed and aggressive patients with Alzheimer's disease.
Vermeiren, Yannick; Van Dam, Debby; Aerts, Tony; Engelborghs, Sebastiaan; De Deyn, Peter P
Depression and aggression in Alzheimer's disease (AD) are 2 of the most severe and prominent neuropsychiatric symptoms (NPS). Altered monoaminergic neurotransmitter system functioning has been implicated in both NPS, although their neurochemical etiology remains to be elucidated. Left frozen hemispheres of 40 neuropathologically confirmed AD patients were regionally dissected. Dichotomization based on depression and aggression scores resulted in depressed/nondepressed (AD + D/AD - D) and aggressive/nonaggressive (AD + Agr/AD - Agr) groups. Concentrations of dopamine, serotonin (5-HT), (nor)epinephrine ((N)E), and respective metabolites were determined using reversed-phase high-performance liquid chromatography. Significantly lower 3-methoxy-4-hydroxyphenylglycol (MHPG) and higher homovanillic acid levels were observed in Brodmann area (BA) 9 and 10 of AD + D compared with AD - D. In AD + Agr, 5-hydroxy-3-indoleacetic acid (5-HIAA) levels in BA9, 5-HIAA to 5-HT ratios in BA11, and MHPG, NE, and 5-HIAA levels in the hippocampus were significantly decreased compared with AD - Agr. These findings indicate that brain region-specific altered monoamines and metabolites may contribute to the occurrence of depression and aggression in AD. PMID:24997673
Traumatic brain injury alters expression of hippocampal microRNAs: potential regulators of multiple pathophysiological processes.
Redell, John B; Liu, Yin; Dash, Pramod K
Multiple cellular, molecular, and biochemical changes contribute to outcome after traumatic brain injury (TBI). MicroRNAs (miRNAs) are known to influence many important cellular processes, including proliferation, apoptosis, neurogenesis, angiogenesis, and morphogenesis, all processes that are involved in TBI pathophysiology. However, it has not yet been determined whether miRNA expression is altered after TBI. In the present study, we used a microarray platform to examine changes in the hippocampal expression levels of 444 verified rodent miRNAs at 3 and 24 hr after controlled cortical impact injury. Our analysis found 50 miRNAs exhibited decreased expression levels and 35 miRNAs exhibited increased expression levels in the hippocampus after injury. We extended the microarray findings using quantitative polymerase chain reaction analysis for a subset of the miRNAs with altered expression levels (miR-107, -130a, -223, -292-5p, -433-3p, -451, -541, and -711). Bioinformatic analysis of the predicted targets for this panel of miRNAs revealed an overrepresentation of proteins involved in several biological processes and functions known to be initiated after injury, including signal transduction, transcriptional regulation, proliferation, and differentiation. Our results indicate that multiple protein targets and biological processes involved in TBI pathophysiology may be regulated by miRNAs. PMID:19021292
Altered sleep composition after traumatic brain injury does not affect declarative sleep-dependent memory consolidation
Mantua, Janna; Mahan, Keenan M.; Henry, Owen S.; Spencer, Rebecca M. C.
Individuals with a history of traumatic brain injury (TBI) often report sleep disturbances, which may be caused by changes in sleep architecture or reduced sleep quality (greater time awake after sleep onset, poorer sleep efficiency, and sleep stage proportion alterations). Sleep is beneficial for memory formation, and herein we examine whether altered sleep physiology following TBI has deleterious effects on sleep-dependent declarative memory consolidation. Participants learned a list of word pairs in the morning or evening, and recall was assessed 12-h later, following an interval awake or with overnight sleep. Young adult participants (18–22 years) were assigned to one of four experimental groups: TBI Sleep (n = 14), TBI Wake (n = 12), non-TBI Sleep (n = 15), non-TBI Wake (n = 15). Each TBI participant was >1 year post-injury. Sleep physiology was measured with polysomnography. Memory consolidation was assessed by comparing change in word-pair recall over 12-h intersession intervals. The TBI group spent a significantly greater proportion of the night in SWS than the non-TBI group at the expense of NREM1. The TBI group also had marginally lower EEG delta power during SWS in the central region. Intersession changes in recall were greater for intervals with sleep than without sleep in both groups. However, despite abnormal sleep stage proportions for individuals with a TBI history, there was no difference in the intersession change in recall following sleep for the TBI and non-TBI groups. In both Sleep groups combined, there was a positive correlation between Intersession Change and the proportion of the night in NREM2 + SWS. Overall, sleep composition is altered following TBI but such deficits do not yield insufficiencies in sleep-dependent memory consolidation. PMID:26097451
Altered sleep composition after traumatic brain injury does not affect declarative sleep-dependent memory consolidation.
Mantua, Janna; Mahan, Keenan M; Henry, Owen S; Spencer, Rebecca M C
Individuals with a history of traumatic brain injury (TBI) often report sleep disturbances, which may be caused by changes in sleep architecture or reduced sleep quality (greater time awake after sleep onset, poorer sleep efficiency, and sleep stage proportion alterations). Sleep is beneficial for memory formation, and herein we examine whether altered sleep physiology following TBI has deleterious effects on sleep-dependent declarative memory consolidation. Participants learned a list of word pairs in the morning or evening, and recall was assessed 12-h later, following an interval awake or with overnight sleep. Young adult participants (18-22 years) were assigned to one of four experimental groups: TBI Sleep (n = 14), TBI Wake (n = 12), non-TBI Sleep (n = 15), non-TBI Wake (n = 15). Each TBI participant was >1 year post-injury. Sleep physiology was measured with polysomnography. Memory consolidation was assessed by comparing change in word-pair recall over 12-h intersession intervals. The TBI group spent a significantly greater proportion of the night in SWS than the non-TBI group at the expense of NREM1. The TBI group also had marginally lower EEG delta power during SWS in the central region. Intersession changes in recall were greater for intervals with sleep than without sleep in both groups. However, despite abnormal sleep stage proportions for individuals with a TBI history, there was no difference in the intersession change in recall following sleep for the TBI and non-TBI groups. In both Sleep groups combined, there was a positive correlation between Intersession Change and the proportion of the night in NREM2 + SWS. Overall, sleep composition is altered following TBI but such deficits do not yield insufficiencies in sleep-dependent memory consolidation. PMID:26097451
Inhibition of Acetylcholinesterase Modulates NMDA Receptor Antagonist Mediated Alterations in the Developing Brain
Bendix, Ivo; Serdar, Meray; Herz, Josephine; von Haefen, Clarissa; Nasser, Fatme; Rohrer, Benjamin; Endesfelder, Stefanie; Felderhoff-Mueser, Ursula; Spies, Claudia D.; Sifringer, Marco
Exposure to N-methyl-d-aspartate (NMDA) receptor antagonists has been demonstrated to induce neurodegeneration in newborn rats. However, in clinical practice the use of NMDA receptor antagonists as anesthetics and sedatives cannot always be avoided. The present study investigated the effect of the indirect cholinergic agonist physostigmine on neurotrophin expression and the extracellular matrix during NMDA receptor antagonist induced injury to the immature rat brain. The aim was to investigate matrix metalloproteinase (MMP)-2 activity, as well as expression of tissue inhibitor of metalloproteinase (TIMP)-2 and brain-derived neurotrophic factor (BDNF) after co-administration of the non-competitive NMDA receptor antagonist MK801 (dizocilpine) and the acetylcholinesterase (AChE) inhibitor physostigmine. The AChE inhibitor physostigmine ameliorated the MK801-induced reduction of BDNF mRNA and protein levels, reduced MK801-triggered MMP-2 activity and prevented decreased TIMP-2 mRNA expression. Our results indicate that AChE inhibition may prevent newborn rats from MK801-mediated brain damage by enhancing neurotrophin-associated signaling pathways and by modulating the extracellular matrix. PMID:24595240
Cerebral blood volume changes during brain activation
Krieger, Steffen Norbert; Streicher, Markus Nikolar; Trampel, Robert; Turner, Robert
Cerebral blood volume (CBV) changes significantly with brain activation, whether measured using positron emission tomography, functional magnetic resonance imaging (fMRI), or optical microscopy. If cerebral vessels are considered to be impermeable, the contents of the skull incompressible, and the skull itself inextensible, task- and hypercapnia-related changes of CBV could produce intolerable changes of intracranial pressure. Because it is becoming clear that CBV may be useful as a well-localized marker of neural activity changes, a resolution of this apparent paradox is needed. We have explored the idea that much of the change in CBV is facilitated by exchange of water between capillaries and surrounding tissue. To this end, we developed a novel hemodynamic boundary-value model and found approximate solutions using a numerical algorithm. We also constructed a macroscopic experimental model of a single capillary to provide biophysical insight. Both experiment and theory model capillary membranes as elastic and permeable. For a realistic change of input pressure, a relative pipe volume change of 21±5% was observed when using the experimental setup, compared with the value of approximately 17±1% when this quantity was calculated from the mathematical model. Volume, axial flow, and pressure changes are in the expected range. PMID:22569192
Differences in functional brain connectivity alterations associated with cerebral amyloid deposition in amnestic mild cognitive impairment.
Yi, Dahyun; Choe, Young Min; Byun, Min Soo; Sohn, Bo Kyung; Seo, Eun Hyun; Han, Jiyoung; Park, Jinsick; Woo, Jong Inn; Lee, Dong Young
Despite potential implications for the early detection of impending Alzheimer's disease (AD), very little is known about the differences of large-scale brain networks between amnestic mild cognitive impairment (aMCI) with high cerebral amyloid-beta protein (A?) deposition (i.e., aMCI+) and aMCI with no or very little A? deposition (i.e., aMCI-). We first aimed to extend the current literature on altering intrinsic functional connectivity (FC) of the default mode network (DMN) and salience network (SN) from cognitively normal (CN) to AD dementia. Second, we further examined the differences of the DMN and the SN between aMCI-, aMCI+, and CN. Forty-three older adult (12 CN, 10 aMCI+, 10 aMCI-, and 11 AD dementia) subjects were included. All participants received comprehensive clinical and neuropsychological assessment, resting-state functional magnetic resonance imaging, structural MRI, and Pittsburgh compound-B-PET scans. FC data were preprocessed using multivariate exploratory linear optimized decomposition into independent components of FMRIB's Software Library. Group comparisons were carried out using the "dual-regression" approach. In addition, to verify presence of gray matter volume changes with intrinsic functional network alterations, voxel-based morphometry was performed on the acquired T1-weighted data. As expected, AD dementia participants exhibited decreased FC in the DMN compared to CN (particularly in the precuneus and cingulate gyrus). The degree of alteration in the DMN in aMCI+ compared to CN was intermediate to that of AD. In contrast, aMCI- exhibited increased FC in the DMN compared to CN (primarily in the precuneus) as well as aMCI+. In terms of the SN, aMCI- exhibited decreased FC compared to both CN and aMCI+ particularly in the inferior frontal gyrus. FC within the SN in aMCI+ and AD did not differ from CN. Compared to CN, aMCI- showed atrophy in bilateral superior temporal gyri whereas aMCI+ showed atrophy in right precuneus. The results indicate that despite the similarity in cross-sectional cognitive features, aMCI- has quite different functional brain connectivity compared to aMCI+. PMID:25745400
Brain studies may alter long-held concepts about likely causes of some voice disorders
Not Available
Two voice disorders long considered to be psychological problems, stuttering and spasmodic dysphonia, have been shown in many persons to have a neurophysiological basis. Investigators at the 155th national meeting of the American Association for the Advancement of Science, in San Francisco, described their findings, which are based on new analytic techniques. The research is being done at the Dallas Center for Vocal Motor Control, Callier Center for Communication Disorders, University of Texas at Dallas Health Science Center. The technology employed to learn what's wrong with the brains, rather than the psyches, of persons with certain speech disorders includes magnetic resonance imaging (MRI), brain electrical activity mapping (BEAM), and single photon emission computerized tomography (SPECT). The results of applying these techniques are combined with quantitative behavioral measures of vocal and nonvocal motor control, language performance, and cognition to arrive at a better understanding of the problem.
Alpha- and gamma- tocopherol prevent age-related transcriptional alterations in the heart and brain of mice
Technology Transfer Automated Retrieval System (TEKTRAN)
To investigate the global effects of vitamin E supplementation on aging, we used high density oligonucleotide arrays to measure transcriptional alterations in the heart and brain (neocortex) of 30-month-old B6C3F1 mice supplemented with alpha- and gamma-tocopherol since middle age (15 months). Gene ...
Structural brain alterations in subjects at high-risk of psychosis: A voxel-based morphometric study
Gaser, Christian
Structural brain alterations in subjects at high-risk of psychosis: A voxel-based morphometric Available online 25 April 2008 Abstract Forty Untreated high-risk (HR) individuals for psychosis and 75 disease of schizophrenia. © 2008 Elsevier B.V. All rights reserved. Keywords: Prodromal psychosis; Imaging
Chemical intervention during prenatal or postnatal ontogeny can result in complex biochemical, morphological and behavioral alterations in brain development (Suzuki, 1980; Miller and O'Callaghan, 1984; Rodier, 1986; Ruppert, 1986). s has been shown at this conference (e.g. by Ham...
Alpha2 adrenergic challenge with guanfacine one month after mild traumatic brain injury: Altered working memory and BOLD response
Thomas W. McAllister; Brenna C. McDonald; Laura A. Flashman; Richard B. Ferrell; Tor D. Tosteson; Norman N. Yanofsky; Margaret R. Grove; Andrew J. Saykin
Alterations in working memory (WM) are common after traumatic brain injury (TBI). Frontal catecholaminergic systems, including the alpha-2 adrenergic system, modulate WM function and may be affected in TBI. We hypothesized that administration of an alpha-2 adrenergic agonist might improve WM after mild TBI (MTBI). Thirteen individuals with MTBI 1month after injury and 14 healthy controls (HC) were challenged with
Exposure to vehicle emissions results in altered blood brain barrier permeability and expression of matrix metalloproteinases and tight junction proteins in mice
Background Traffic-generated air pollution-exposure is associated with adverse effects in the central nervous system (CNS) in both human exposures and animal models, including neuroinflammation and neurodegeneration. While alterations in the blood brain barrier (BBB) have been implicated as a potential mechanism of air pollution-induced CNS pathologies, pathways involved have not been elucidated. Objectives To determine whether inhalation exposure to mixed vehicle exhaust (MVE) mediates alterations in BBB permeability, activation of matrix metalloproteinases (MMP) -2 and ?9, and altered tight junction (TJ) protein expression. Methods Apolipoprotein (Apo) E?/? and C57Bl6 mice were exposed to either MVE (100 ?g/m3 PM) or filtered air (FA) for 6 hr/day for 30 days and resulting BBB permeability, expression of ROS, TJ proteins, markers of neuroinflammation, and MMP activity were assessed. Serum from study mice was applied to an in vitro BBB co-culture model and resulting alterations in transport and permeability were quantified. Results MVE-exposed Apo E?/? mice showed increased BBB permeability, elevated ROS and increased MMP-2 and ?9 activity, compared to FA controls. Additionally, cerebral vessels from MVE-exposed mice expressed decreased levels of TJ proteins, occludin and claudin-5, and increased levels of inducible nitric oxide synthase (iNOS) and interleukin (IL)-1? in the parenchyma. Serum from MVE-exposed animals also resulted in increased in vitro BBB permeability and altered P-glycoprotein transport activity. Conclusions These data indicate that inhalation exposure to traffic-generated air pollutants promotes increased MMP activity and degradation of TJ proteins in the cerebral vasculature, resulting in altered BBB permeability and expression of neuroinflammatory markers. PMID:24344990
Maternal Inflammation Contributes to Brain Overgrowth and Autism-Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells
Le Belle, Janel E.; Sperry, Jantzen; Ngo, Amy; Ghochani, Yasmin; Laks, Dan R.; López-Aranda, Manuel; Silva, Alcino J.; Kornblum, Harley I.
Summary A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX)-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species. PMID:25418720
Experimental human endotoxemia enhances brain activity during social cognition.
Kullmann, Jennifer S; Grigoleit, Jan-Sebastian; Wolf, Oliver T; Engler, Harald; Oberbeck, Reiner; Elsenbruch, Sigrid; Forsting, Michael; Schedlowski, Manfred; Gizewski, Elke R
Acute peripheral inflammation with corresponding increases in peripheral cytokines affects neuropsychological functions and induces depression-like symptoms. However, possible effects of increased immune responses on social cognition remain unknown. Therefore, this study investigated the effects of experimentally induced acute inflammation on performance and neural responses during a social cognition task assessing Theory of Mind (ToM) ability. In this double-blind randomized crossover functional magnetic resonance imaging study, 18 healthy right-handed male volunteers received an injection of bacterial lipopolysaccharide (LPS; 0.4 ng/kg) or saline, respectively. Plasma levels of pro- and anti-inflammatory cytokines as well as mood ratings were analyzed together with brain activation during a validated ToM task (i.e. Reading the Mind in the Eyes Test). LPS administration induced pronounced transient increases in pro- (IL-6, TNF-?) and anti-inflammatory (IL-10, IL-1ra) cytokines as well as decreases in mood. Social cognition performance was not affected by acute inflammation. However, altered neural activity was observed during the ToM task after LPS administration, reflected by increased responses in the fusiform gyrus, temporo-parietal junction, superior temporal gyrus and precuneus. The increased task-related neural responses in the LPS condition may reflect a compensatory strategy or a greater social cognitive processing as a function of sickness. PMID:23547245
Experimental human endotoxemia enhances brain activity during social cognition
Kullmann, Jennifer S.; Grigoleit, Jan-Sebastian; Wolf, Oliver T.; Engler, Harald; Oberbeck, Reiner; Elsenbruch, Sigrid; Forsting, Michael; Gizewski, Elke R.
Acute peripheral inflammation with corresponding increases in peripheral cytokines affects neuropsychological functions and induces depression-like symptoms. However, possible effects of increased immune responses on social cognition remain unknown. Therefore, this study investigated the effects of experimentally induced acute inflammation on performance and neural responses during a social cognition task assessing Theory of Mind (ToM) ability. In this double-blind randomized crossover functional magnetic resonance imaging study, 18 healthy right-handed male volunteers received an injection of bacterial lipopolysaccharide (LPS; 0.4 ng/kg) or saline, respectively. Plasma levels of pro- and anti-inflammatory cytokines as well as mood ratings were analyzed together with brain activation during a validated ToM task (i.e. Reading the Mind in the Eyes Test). LPS administration induced pronounced transient increases in pro- (IL-6, TNF-?) and anti-inflammatory (IL-10, IL-1ra) cytokines as well as decreases in mood. Social cognition performance was not affected by acute inflammation. However, altered neural activity was observed during the ToM task after LPS administration, reflected by increased responses in the fusiform gyrus, temporo-parietal junction, superior temporal gyrus and precuneus. The increased task-related neural responses in the LPS condition may reflect a compensatory strategy or a greater social cognitive processing as a function of sickness. PMID:23547245
Brain Activation during Working Memory after Traumatic Brain Injury in Children
Mary R. Newsome; Randall S. Scheibel; Jill V. Hunter; Zhiyue J. Wang; Zili Chu; Xiaoqi Li; Harvey S. Levin
Eight children with moderate to severe traumatic brain injury (TBI) and eight matched, uninjured control children underwent fMRI during an N-back task to test effects of TBI on working memory performance and brain activation. Two patterns in the TBI group were observed. Patients whose criterion performance was reached at lower memory loads than control children demonstrated less extensive frontal and
Anxiolytic activity of a brain delivery system for GABA
W. R. Anderson; J. W. Simpkins; P. A. Woodard; D. Winwood; W. C. Stern; N. Bodor
We evaluated the anxiolytic property of a brain-specific gamma-aminobutyric acid delivery system (GABA-CDS) in male rats by means of a drink-foot shock conflict procedure. Brain-specific delivery of the active compound was achieved by combination of GABA benzyl ester with an interconvertible dihydropyridine?pyridinium salt carrier, which is "locked in" to the brain upon its oxidation. Pharmacokinetic studies revealed that the hydrophilic
Altered Water Diffusivity in Mouse AQP4-/- Brain During Development Using Diffusion Tensor Imaging
Yang, Gi Eun
2000). "Aquaporin-4 deletion in mice reduces brain edemaAquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema."Aquaporin-4 gene deletion in mice increases focal edema associated with staphylococcal brain
Acute focal brain damage alters mitochondrial dynamics and autophagy in axotomized neurons
Cavallucci, V; Bisicchia, E; Cencioni, M T; Ferri, A; Latini, L; Nobili, A; Biamonte, F; Nazio, F; Fanelli, F; Moreno, S; Molinari, M; Viscomi, M T; D'Amelio, M
Mitochondria are key organelles for the maintenance of life and death of the cell, and their morphology is controlled by continual and balanced fission and fusion dynamics. A balance between these events is mandatory for normal mitochondrial and neuronal function, and emerging evidence indicates that mitochondria undergo extensive fission at an early stage during programmed cell death in several neurodegenerative diseases. A pathway for selective degradation of damaged mitochondria by autophagy, known as mitophagy, has been described, and is of particular importance to sustain neuronal viability. In the present work, we analyzed the effect of autophagy stimulation on mitochondrial function and dynamics in a model of remote degeneration after focal cerebellar lesion. We provided evidence that lesion of a cerebellar hemisphere causes mitochondria depolarization in axotomized precerebellar neurons associated with PTEN-induced putative kinase 1 accumulation and Parkin translocation to mitochondria, block of mitochondrial fusion by Mfn1 degradation, increase of calcineurin activity and dynamin-related protein 1 translocation to mitochondria, and consequent mitochondrial fission. Here we suggest that the observed neuroprotective effect of rapamycin is the result of a dual role: (1) stimulation of autophagy leading to damaged mitochondria removal and (2) enhancement of mitochondria fission to allow their elimination by mitophagy. The involvement of mitochondrial dynamics and mitophagy in brain injury, especially in the context of remote degeneration after acute focal brain damage, has not yet been investigated, and these findings may offer new target for therapeutic intervention to improve functional outcomes following acute brain damage. PMID:25429622
The Bile Acid-Sensitive Ion Channel (BASIC) Is Activated by Alterations of Its Membrane Environment
Schmidt, Axel; Lenzig, Pia; Oslender-Bujotzek, Adrienne; Kusch, Jana; Dias Lucas, Susana; Gründer, Stefan; Wiemuth, Dominik
The bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC family of ion channels. Channels of this family are characterized by a common structure, their physiological functions and modes of activation, however, are diverse. Rat BASIC is expressed in brain, liver and intestinal tract and activated by bile acids. The physiological function of BASIC and its mechanism of bile acid activation remain a puzzle. Here we addressed the question whether amphiphilic bile acids activate BASIC by directly binding to the channel or indirectly by altering the properties of the surrounding membrane. We show that membrane-active substances other than bile acids also affect the activity of BASIC and that activation by bile acids and other membrane-active substances is non-additive, suggesting that BASIC is sensitive for changes in its membrane environment. Furthermore based on results from chimeras between BASIC and ASIC1a, we show that the extracellular and the transmembrane domains are important for membrane sensitivity. PMID:25360526
Deletion of Rictor in Brain and Fat Alters Peripheral Clock Gene Expression and Increases Blood Pressure.
Drägert, Katja; Bhattacharya, Indranil; Pellegrini, Giovanni; Seebeck, Petra; Azzi, Abdelhalim; Brown, Steven A; Georgiopoulou, Stavroula; Held, Ulrike; Blyszczuk, Przemyslaw; Arras, Margarete; Humar, Rok; Hall, Michael N; Battegay, Edouard; Haas, Elvira
The mammalian target of rapamycin complex 2 (mTORC2) contains the essential protein RICTOR and is activated by growth factors. mTORC2 in adipose tissue contributes to the regulation of glucose and lipid metabolism. In the perivascular adipose tissue, mTORC2 ensures normal vascular reactivity by controlling expression of inflammatory molecules. To assess whether RICTOR/mTORC2 contributes to blood pressure regulation, we applied a radiotelemetry approach in control and Rictor knockout (Rictor(aP2KO)) mice generated using adipocyte protein-2 gene promoter-driven CRE recombinase expression to delete Rictor. The 24-hour mean arterial pressure was increased in Rictor(aP2KO) mice, and the physiological decline in mean arterial pressure during the dark period was impaired. In parallel, heart rate and locomotor activity were elevated during the dark period with a pattern similar to blood pressure changes. This phenotype was associated with mild cardiomyocyte hypertrophy, decreased cardiac natriuretic peptides, and their receptor expression in adipocytes. Moreover, clock gene expression was reduced or phase-shifted in perivascular adipose tissue. No differences in clock gene expression were observed in the master clock suprachiasmatic nucleus, although Rictor gene expression was also lower in brain of Rictor(aP2KO) mice. Thus, this study highlights the importance of RICTOR/mTORC2 for interactions between vasculature, adipocytes, and brain to tune physiological outcomes, such as blood pressure and locomotor activity. PMID:26101345
Brain Activation during Sight Gags and Language-Dependent Humor
Allman, John M.
Brain Activation during Sight Gags and Language-Dependent Humor Karli K. Watson1 , Benjamin J humor (sight gags) and language- based humor. Our findings indicate that the brain networks re- cruited 2003). Humor also has a strong social aspect, and in fact, measure- ments of extroversion in human
McCluskey, Matthew
OPTICAL IMAGING OF NEURAL AND HEMODYNAMIC BRAIN ACTIVITY By JENNIFER LYNN SCHEI A dissertation his brain. His generosity has provided me with endless op- portunities to grow as a scientist in which, who thoroughly read every piece of writing I sent and asked questions about the content
Linking neocortical, cognitive, and genetic variability in autism with alterations of brain plasticity: the Trigger-Threshold-Target model.
Mottron, Laurent; Belleville, Sylvie; Rouleau, Guy A; Collignon, Olivier
The phenotype of autism involves heterogeneous adaptive traits (strengths vs. disabilities), different domains of alterations (social vs. non-social), and various associated genetic conditions (syndromic vs. nonsyndromic autism). Three observations suggest that alterations in experience-dependent plasticity are an etiological factor in autism: (1) the main cognitive domains enhanced in autism are controlled by the most plastic cortical brain regions, the multimodal association cortices; (2) autism and sensory deprivation share several features of cortical and functional reorganization; and (3) genetic mutations and/or environmental insults involved in autism all appear to affect developmental synaptic plasticity, and mostly lead to its upregulation. We present the Trigger-Threshold-Target (TTT) model of autism to organize these findings. In this model, genetic mutations trigger brain reorganization in individuals with a low plasticity threshold, mostly within regions sensitive to cortical reallocations. These changes account for the cognitive enhancements and reduced social expertise associated with autism. Enhanced but normal plasticity may underlie non-syndromic autism, whereas syndromic autism may occur when a triggering mutation or event produces an altered plastic reaction, also resulting in intellectual disability and dysmorphism in addition to autism. Differences in the target of brain reorganization (perceptual vs. language regions) account for the main autistic subgroups. In light of this model, future research should investigate how individual and sex-related differences in synaptic/regional brain plasticity influence the occurrence of autism. PMID:25155242
Nanotools for Neuroscience and Brain Activity Mapping
Alivisatos, A. Paul
Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We ...
Modifying caspase-3 activity by altering allosteric networks.
Cade, Christine; Swartz, Paul; MacKenzie, Sarah H; Clark, A Clay
Caspases have several allosteric sites that bind small molecules or peptides. Allosteric regulators are known to affect caspase enzyme activity, in general, by facilitating large conformational changes that convert the active enzyme to a zymogen-like form in which the substrate-binding pocket is disordered. Mutations in presumed allosteric networks also decrease activity, although large structural changes are not observed. Mutation of the central V266 to histidine in the dimer interface of caspase-3 inactivates the enzyme by introducing steric clashes that may ultimately affect positioning of a helix on the protein surface. The helix is thought to connect several residues in the active site to the allosteric dimer interface. In contrast to the effects of small molecule allosteric regulators, the substrate-binding pocket is intact in the mutant, yet the enzyme is inactive. We have examined the putative allosteric network, in particular the role of helix 3, by mutating several residues in the network. We relieved steric clashes in the context of caspase-3(V266H), and we show that activity is restored, particularly when the restorative mutation is close to H266. We also mimicked the V266H mutant by introducing steric clashes elsewhere in the allosteric network, generating several mutants with reduced activity. Overall, the data show that the caspase-3 native ensemble includes the canonical active state as well as an inactive conformation characterized by an intact substrate-binding pocket, but with an altered helix 3. The enzyme activity reflects the relative population of each species in the native ensemble. PMID:25343534
Regional Brain Activation during Hypoglycemia in Type 1 Diabetes
Musen, Gail; Simonson, Donald C.; Bolo, Nicolas R.; Driscoll, Amy; Weinger, Katie; Raji, Annaswamy; Théberge, Jean; Renshaw, Perry F.; Jacobson, Alan M.
Context: Mechanisms underlying the brain response to hypoglycemia are not well understood. Objective: Our objective was to determine the blood glucose level at which the hypothalamus and other brain regions are activated in response to hypoglycemia in type 1 diabetic patients and control subjects. Design: This was a cross-sectional study evaluating brain activity using functional magnetic resonance imaging in conjunction with a hyperinsulinemic hypoglycemic clamp to lower glucose from euglycemia (90 mg/dl) to hypoglycemia (50 mg/dl). Setting: The study was performed at the Brain Imaging Center in the McLean Hospital. Study Participants: Seven type 1 diabetic patients between 18 and 50 yr old and six matched control subjects were included in the study. Intervention: Hyperinsulinemic hypoglycemic clamp was performed. Main Outcome Measures: Blood glucose level at peak hypothalamic activation, amount of regional brain activity during hypoglycemia in both groups, and difference in regional brain activation between groups were calculated. Results: The hypothalamic region activates at 68 ± 9 mg/dl in control subjects and 76 ± 8 mg/dl in diabetic patients during hypoglycemia induction. Brainstem, anterior cingulate cortex, uncus, and putamen were activated in both groups (P < 0.001). Each group also activated unique brain areas not active in the other group. Conclusions: This application of functional magnetic resonance imaging can be used to identify the glucose level at which the hypothalamus is triggered in response to hypoglycemia and whether this threshold differs across patient populations. This study suggests that a core network of brain regions is recruited during hypoglycemia in both diabetic patients and control subjects. PMID:18198228
Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1
Dawson, N; Kurihara, M; Thomson, D M; Winchester, C L; McVie, A; Hedde, J R; Randall, A D; Shen, S; Seymour, P A; Hughes, Z A; Dunlop, J; Brown, J T; Brandon, N J; Morris, B J; Pratt, J A
Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal–PFC connectivity. Altered hippocampal–PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1–PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity. PMID:25989143
Anatomical atlas-guided diffuse optical tomography of brain activation
Custo, Anna
We describe a neuroimaging protocol that utilizes an anatomical atlas of the human head to guide diffuse optical tomography of human brain activation. The protocol is demonstrated by imaging the hemodynamic response to ...
Oppositional Children Differ from Healthy Children in Frontal Brain Activation
Lioba Baving; Manfred Laucht; Martin H. Schmidt
An atypical EEG pattern of frontal brain activation, which has been found in children and adults with emotional disorders, also is hypothesized to be present in disruptive behavior disorders. One hundred nineteen children (4\\u000a
BRAIN NETWORKS. Correlated gene expression supports synchronous activity in brain networks.
Richiardi, Jonas; Altmann, Andre; Milazzo, Anna-Clare; Chang, Catie; Chakravarty, M Mallar; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Lemaître, Hervé; Mann, Karl F; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomáš; Pausova, Zdenka; Rietschel, Marcella; Robbins, Trevor W; Smolka, Michael N; Spanagel, Rainer; Ströhle, Andreas; Schumann, Gunter; Hawrylycz, Mike; Poline, Jean-Baptiste; Greicius, Michael D
During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function. PMID:26068849
Altered AMP deaminase activity may extend postmortem glycolysis.
England, E M; Matarneh, S K; Scheffler, T L; Wachet, C; Gerrard, D E
Postmortem energy metabolism drives hydrogen accumulation in muscle and results in a fairly constant ultimate pH. Extended glycolysis results in adverse pork quality and may be possible with greater adenonucleotide availability postmortem. We hypothesized that slowing adenonucleotide removal by reducing AMP deaminase activity would extend glycolysis and lower the ultimate pH of muscle. Longissimus muscle samples were incorporated into an in vitro system that mimics postmortem glycolysis with or without pentostatin, an AMP deaminase inhibitor. Pentostatin lowered ultimate pH and increased lactate and glucose 6-phosphate with time. Based on these results and that AMPK ?3(R200Q) mutated pigs (RN(-)) produce low ultimate pH pork, we hypothesized AMP deaminase abundance and activity would be lower in RN(-) muscle than wild-type. RN(-) muscle contained lower AMP deaminase abundance and activity. These data show that altering adenonucleotide availability postmortem can extend postmortem pH decline and suggest that AMP deaminase activity may, in part, contribute to the low ultimate pH observed in RN(-) pork. PMID:25498483
Hyperammonemia, brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paracetamol intoxication
Camila Scorticati; Juan P. Prestifilippo; Francisco X. Eizayaga; José L. Castro; Salvador Romay; María A. Fernández; Abraham Lemberg; Juan C. Perazzo
AIM: To study the blood-brain barrier integrity, brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS: Adults male Wistar rats were divided into four groups. Group I: sham operation; II: Prehepatic portal hypertension, produced by partial portal vein ligation; III: Acetaminophen intoxication and IV: Prehepatic portal hypertension plus acetaminophen.
Effects of cyclodiene compounds on calcium pump activity in rat brain and heart.
Mehrotra, B D; Moorthy, K S; Reddy, S R; Desaiah, D
The in vitro and in vivo effects of aldrin, dieldrin, and endrin on calmodulin regulated Ca2+-pump activity in rat brain synaptosomes and heart sarcoplasmic reticulum were investigated. All the 3 cyclodiene compounds inhibited both brain synaptosomal and heart sarcoplasmic reticulum Ca2+-pump activity in vitro in a concentration dependent manner. Calmodulin depleted Ca2+-pump activity was insensitive to the action of toxic compounds. Oral administration of pesticides (0.5-10 mg/kg) to rats similarly decreased the Ca2+-pump activity, in addition to decreasing the levels of calmodulin of both brain and heart thus indicating disruption in membrane Ca2+ transport mechanisms. Exogenous addition of calmodulin (1-20 micrograms) could effectively reverse the pesticide induced inhibition. Ca2+-pump activity is more sensitive to the 3 cyclodiene compounds in brain than in heart. The results of the present study indicate that the cyclodiene compounds may produce neurotoxic effects by altering calmodulin regulated calcium dependent events in neurons. PMID:2536969
Multiple toxic doses of methamphetamine alter neurotensin concentrations in various region of the rat brain
Hanson, G.R.; Merchant, K.; Gibb, J.W.; Letter, A.A.
The authors have previously reported that multiple high doses of methamphetamine (METH) alter neuronal monoamine metabolism and release. Recently, Hokfelt et al. showed that neurotensin, a tridecapeptide, has neurotransmitter properties which may be involved with DA neuronal activity. In the present study they investigated the possible effects of METH on the CNS neurotensin system. Five doses of METH (15 mg/kg) were administered every 6 h; control and treated rats were sacrificed 18 h after the last dose and concentrations of neurotensin-like immuno-reactivity (NTLI) were measured by radioimmunoassay. NTLI was elevated 200-300% in the nucleus accumbens, neostriatum, and substantia nigra; 30-40% increases in NTLI were measured in the hippocampus and hypothalamus. No change was observed in amygdala, A-10 or periaqueductal gray. In contrast to the above measured areas, the frontal lobe and olfactory bulb showed decreases of 25-35%. These findings demonstrate that METH treatment alters the activities of several CNS neurotensin systems, possibly due to the influence of this drug on DA pathways. The variability in the type and magnitude of these responses suggests that DA and neurotensin systems interact by more than one mechanism.
Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks.
Dawson, Neil; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A
Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia. PMID:24492765
Subanesthetic Ketamine Treatment Promotes Abnormal Interactions between Neural Subsystems and Alters the Properties of Functional Brain Networks
Dawson, Neil; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A
Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia. PMID:24492765
Linking neuronal brain activity to the glucose metabolism
Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. Methods First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Results Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. Conclusions The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported. PMID:23988084
Brain Activity Patterns Uniquely Supporting Visual Feature Integration after Traumatic Brain Injury
Raja Beharelle, Anjali; Tisserand, Danielle; Stuss, Donald T.; McIntosh, Anthony R.; Levine, Brian
Traumatic brain injury (TBI) patients typically respond more slowly and with more variability than controls during tasks of attention requiring speeded reaction time. These behavioral changes are attributable, at least in part, to diffuse axonal injury (DAI), which affects integrated processing in distributed systems. Here we use a multivariate method sensitive to distributed neural activity to compare brain activity patterns of patients with chronic phase moderate to-severe TBI to those of controls during performance on a visual feature integration task assessing complex attentional processes that has previously shown sensitivity to TBI. The TBI patients were carefully screened to be free of large focal lesions that can affect performance and brain activation independently of DAI. The task required subjects to hold either one or three features of a Target in mind while suppressing responses to distracting information. In controls, the multi-feature condition activated a distributed network including limbic, prefrontal, and medial temporal structures. TBI patients engaged this same network in the single-feature and baseline conditions. In multi-feature presentations, TBI patients alone activated additional frontal, parietal, and occipital regions. These results are consistent with neuroimaging studies using tasks assessing different cognitive domains, where increased spread of brain activity changes was associated with TBI. Our results also extend previous findings that brain activity for relatively moderate task demands in TBI patients is similar to that associated with of high task demands in controls. PMID:22180740
Pharmacological activity of metal binding agents that alter copper bioavailability
Helsel, Marian E.
Iron, copper and zinc are required nutrients for many organisms but also potent toxins if misappropriated. An overload of any of these metals can be cytotoxic and ultimately lead to organ failure, whereas deficiencies can result in anemia, weakened immune system function, and other medical conditions. Cellular metal imbalances have been implicated in neurodegenerative diseases, cancer and infection. It is therefore critical for living organisms to maintain careful control of both the total levels and subcellular distributions of these metals to maintain healthy function. This perspective explores several strategies envisioned to alter the bioavailability of metal ions by using synthetic metal-binding agents targeted for diseases where misappropriated metal ions are suspected of exacerbating cellular damage. Specifically, we discuss chemical properties that influence the pharmacological outcome of a subset of metal-binding agents known as ionophores, and review several examples that have shown multiple pharmacological activities in metal-related diseases, with a specific focus on copper. PMID:25797044
Phosphorylation of Yellow Fever Virus NS5 alters methyltransferase activity
Bhattacharya, Dipankar; Hoover, Spencer; Falk, Shaun P.; Weisblum, Bernard; Vestling, Martha; Striker, Rob
Serine/threonine phosphorylation of the nonstructural protein 5 (NS5) is conserved feature of flaviviruses, but the kinase(s) responsible and function(s) remain unknown. Mass spectrometry was used to characterize phosphorylated residues of yellow fever virus (YFV) NS5 expressed in mammalian cells. Multiple different phosphopeptides were detected. Mutational and additional mass spectrometry data implicated serine 56 (S56), a conserved residue near the active site in the NS5 methyltransferase domain, as one of the phosphorylation sites. Methyltransferase activity is required to form a methylated RNA cap structure and for translation of the YFV polyprotein. We show the 2'-O- methylation reaction requires the hydroxyl side chain of S56, and replacement with a negative charge inhibits enzymatic activity. Furthermore mutational alteration of S56, S56A or S56D, prevents amplification in a viral replicon system. Collectively our data suggest phosphorylation of NS5 S56 may act to shut down capping in the viral life cycle. PMID:18757072
Reconstructing visual experiences from brain activity evoked by natural movies
Nishimoto, Shinji; Vu, An T.; Naselaris, Thomas; Benjamini, Yuval; Yu, Bin; Gallant, Jack L.
Summary Quantitative modeling of human brain activity can provide crucial insights about cortical representations [1, 2], and can form the basis for brain decoding devices [3–5]. Recent functional magnetic resonance imaging (fMRI) studies have modeled brain activity elicited by static visual patterns, and have shown that it is possible to reconstruct these images from brain activity measurements [6–8]. However, blood oxygen level dependent (BOLD) signals measured using fMRI are very slow [9], so it has been difficult to model brain activity elicited by dynamic stimuli such as natural movies. Here we present a new motion-energy [10, 11] encoding model that largely overcome this limitation. Our motion-energy model describes fast visual information and slow hemodynamics by separate components. We recorded BOLD signals in occipito-temporal visual cortex of human subjects who passively watched natural movies, and fit the encoding model separately to individual voxels. Visualization of the fit models reveals how early visual areas represent moving stimuli. To demonstrate the power of our approach we also constructed a Bayesian decoder [8], by combining estimated encoding models with a sampled natural movie prior. The decoder provides remarkable reconstructions of natural movies, capturing the spatio-temporal structure of the viewed movie. These results demonstrate that dynamic brain activity measured under naturalistic conditions can be decoded using current fMRI technology. PMID:21945275
Chronic Social Stress in Puberty Alters Appetitive Male Sexual Behavior and Neural Metabolic Activity
Bastida, Christel C.; Puga, Frank; Gonzalez-Lima, Francisco; Jennings, Kimberly J.; Wommack, Joel C.; Delville, Yvon
Repeated social subjugation in early puberty lowers testosterone levels. We used hamsters to investigate the effects of social subjugation on male sexual behavior and metabolic activity within neural systems controlling social and motivational behaviors. Subjugated animals were exposed daily to aggressive adult males in early puberty for postnatal days 28 to 42, while control animals were placed in empty clean cages. On postnatal day 45, they were tested for male sexual behavior in the presence of receptive female. Alternatively, they were tested for mate choice after placement at the base of a Y-maze containing a sexually receptive female in one tip of the maze and an ovariectomized one on the other. Social subjugation did not affect the capacity to mate with receptive females. Although control animals were fast to approach females and preferred ovariectomized individuals, subjugated animals stayed away from them and showed no preference. Cytochrome oxidase activity was reduced within the preoptic area and ventral tegmental area in subjugated hamsters. In addition, the correlation of metabolic activity of these areas with the bed nucleus of the stria terminalis and anterior parietal cortex changed significantly from positive in controls to negative in subjugated animals. These data show that at mid-puberty, while male hamsters are capable of mating, their appetitive sexual behavior is not fully mature and this aspect of male sexual behavior is responsive to social subjugation. Furthermore, metabolic activity and coordination of activity in brain areas related to sexual behavior and motivation was altered by social subjugation. PMID:24852486
Microwave irradiation decreases ATP, increases free [Mg2+], and alters in vivo intracellular reactions in rat brain
Srivastava, Shireesh; Kashiwaya, Yoshihiro; Chen, Xuesong; Geiger, Jonathan D.; Pawlosky, Robert; Veech, Richard L.
Rapid inactivation of metabolism is essential for accurately determining the concentrations of metabolic intermediates in the in vivo state. We compared a broad spectrum of energetic intermediate metabolites and neurotransmitters in brains obtained by microwave irradiation to those obtained by freeze blowing, the most rapid method of extracting and freezing rat brain. The concentrations of many intermediates, cytosolic free NAD(P)+/NAD(P)H ratios, as well as neurotransmitters were not affected by the microwave procedure. However, the brain concentrations of ATP were about 30% lower, whereas those of ADP, AMP, and GDP were higher in the microwave-irradiated compared with the freeze-blown brains. In addition, the hydrolysis of approximately 1 ?mol/g of ATP, a major in vivo Mg2+-binding site, was related to approximately five-fold increase in free [Mg2+] (0.53 ± 0.07 mM in freeze blown vs. 2.91 mM ± 0.48 mM in microwaved brains), as determined from the ratio [citrate]/[isocitrate]. Consequently, many intracellular properties, such as the phosphorylation potential and the ?G' of ATP hydrolysis were significantly altered in microwaved tissue. The determinations of some glycolytic and TCA cycle metabolites, the phosphorylation potential, and the ?G' of ATP hydrolysis do not represent the in vivo state when using microwave-fixed brain tissue. PMID:23013291
Smoking and the developing brain: altered white matter microstructure in attention-deficit/hyperactivity disorder and healthy controls.
van Ewijk, Hanneke; Groenman, Annabeth P; Zwiers, Marcel P; Heslenfeld, Dirk J; Faraone, Stephen V; Hartman, Catharina A; Luman, Marjolein; Greven, Corina U; Hoekstra, Pieter J; Franke, Barbara; Buitelaar, Jan; Oosterlaan, Jaap
Brain white matter (WM) tracts, playing a vital role in the communication between brain regions, undergo important maturational changes during adolescence and young adulthood, a critical period for the development of nicotine dependence. Attention-deficit/hyperactivity disorder (ADHD) is associated with increased smoking and widespread WM abnormalities, suggesting that the developing ADHD brain might be especially vulnerable to effects of smoking. This study aims to investigate the effect of smoking on (WM) microstructure in adolescents and young adults with and without ADHD. Diffusion tensor imaging was performed in an extensively phenotyped sample of nonsmokers (n = 95, 50.5% ADHD), irregular smokers (n = 41, 58.5% ADHD), and regular smokers (n = 50, 82.5% ADHD), aged 14-24 years. A whole-brain voxelwise approach investigated associations of smoking, ADHD and their interaction, with WM microstructure as measured by fractional anisotropy (FA) and mean diffusivity (MD). Widespread alterations in FA and MD were found for regular smokers compared to irregular and nonsmokers, mainly located in the corpus callosum and WM tracts surrounding the basal ganglia. Several regions overlapped with regions of altered FA for ADHD versus controls, albeit in different directions. Irregular and nonsmokers did not differ, and ADHD and smoking did not interact. Results implicate that smoking and ADHD have independent effects on WM microstructure, and possibly do not share underlying mechanisms. Two mechanisms may play a role in the current results. First, smoking may cause alterations in WM microstructure in the maturing brain. Second, pre-existing WM microstructure differences possibly reflect a risk factor for development of a smoking addiction. PMID:25484258
Comparison of laterality index of upper and lower limb movement using brain activated fMRI
NASA Astrophysics Data System (ADS)
Harirchian, Mohammad Hossein; Oghabian, Mohammad Ali; Rezvanizadeh, Alireza; Bolandzadeh, Niousha
Asymmetry of bilateral cerebral function, i.e. laterality, is an important phenomenon in many brain actions such as motor functions. This asymmetry maybe altered in some clinical conditions such as Multiple Sclerosis (MS). The aim of this study was to delineate the laterality differences for upper and lower limbs in healthy subjects to compare this pattern with subjects suffering from MS in advance. Hence 9 Male healthy subjects underwent fMRI assessment, while they were asked to move their limbs in a predetermined pattern. The results showed that hands movement activates the brain with a significant lateralization in pre-motor cortex in comparison with lower limb. Also, dominant hands activate brain more lateralized than the non-dominant hand. In addition, Left basal ganglia were observed to be activated regardless of the hand used, While, These patterns of Brain activation was not detected in lower limbs. We hypothesize that this difference might be attributed to this point that hand is usually responsible for precise and fine voluntary movements, whereas lower limb joints are mainly responsible for locomotion, a function integrating voluntary and automatic bilateral movements.
PATH57 Altered structural and functional network connectivity predicts cognitive function after traumatic brain injury
D Sharp; Powell J Leech R; V Bonnelle; C F Beckmann; X De Boissezon; R Greenwood; K Kinnunen
Traumatic brain injury (TBI) often results in cognitive impairments that limit recovery. The key pathophysiological predictors of recovery are uncertain, but the disruption of brain networks by diffuse axonal injury (DAI) is likely to be important. Here we use MRI to investigate the effect of TBI on structural and functional connections within cognitive brain networks. We studied 21 patients after
Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse
Shimizu, Midori; Tainaka, Hitoshi; Oba, Taro; Mizuo, Keisuke; Umezawa, Masakazu; Takeda, Ken
Background Nanotechnology is developing rapidly throughout the world and the production of novel man-made nanoparticles is increasing, it is therefore of concern that nanomaterials have the potential to affect human health. The purpose of this study was to investigate the effects of maternal exposure to nano-sized anatase titanium dioxide (TiO2) on gene expression in the brain during the developmental period using cDNA microarray analysis combined with Gene Ontology (GO) and Medical Subject Headings (MeSH) terms information. Results Analysis of gene expression using GO terms indicated that expression levels of genes associated with apoptosis were altered in the brain of newborn pups, and those associated with brain development were altered in early age. The genes associated with response to oxidative stress were changed in the brains of 2 and 3 weeks old mice. Changes of the expression of genes associated with neurotransmitters and psychiatric diseases were found using MeSH terms. Conclusion Maternal exposure of mice to TiO2 nanoparticles may affect the expression of genes related to the development and function of the central nervous system. PMID:19640265
Interaction of metabolic stress with chronic mild stress in altering brain cytokines and sucrose preference.
Remus, Jennifer L; Stewart, Luke T; Camp, Robert M; Novak, Colleen M; Johnson, John D
There is growing evidence that metabolic stressors increase an organism's risk of depression. Chronic mild stress is a popular animal model of depression and several serendipitous findings have suggested that food deprivation prior to sucrose testing in this model is necessary to observe anhedonic behaviors. Here, we directly tested this hypothesis by exposing animals to chronic mild stress and used an overnight 2-bottle sucrose test (food ad libitum) on Day 5 and 10, then food and water deprive animals overnight and tested their sucrose consumption and preference in a 1-hr sucrose test the following morning. Approximately 65% of stressed animals consumed sucrose and showed a sucrose preference similar to nonstressed controls in an overnight sucrose test, and 35% showed a decrease in sucrose intake and preference. Following overnight food and water deprivation the previously "resilient" animals showed a significant decrease in sucrose preference and greatly reduced sucrose intake. In addition, we evaluated whether the onset of anhedonia following food and water deprivation corresponds to alterations in corticosterone, epinephrine, circulating glucose, or interleukin-1 beta (IL-1?) expression in limbic brain areas. Although all stressed animals showed adrenal hypertrophy and elevated circulating epinephrine, only stressed animals that were food deprived were hypoglycemic compared with food-deprived controls. Additionally, food and water deprivation significantly increased hippocampus IL-1? while food and water deprivation only increased hypothalamus IL-1? in stress-susceptible animals. These data demonstrate that metabolic stress of food and water deprivation interacts with chronic stressor exposure to induce physiological and anhedonic responses. (PsycINFO Database Record PMID:25914924
Prenatal stress alters microglial development and distribution in postnatal rat brain.
Gómez-González, Beatriz; Escobar, Alfonso
Stress affects microglial function and viability during adulthood and early postnatal life; however, it is unknown whether stress to the pregnant dam might alter offspring microglia. The effects of prenatal stress on microglial development and distribution in the postnatal brain were studied using Wistar rats. Prenatal stress consisting of 20 min of forced swimming occurred on embryonic days 10-20. On postnatal days 1 and 10, stressed and control pups were killed. Microglia were identified using Griffonia simplicifolia lectin and quantified in the whole encephalon. In addition, plasma corticosterone was measured in dams at embryonic day 20, and in pups on postnatal days 1 and 10. At postnatal day 1, there was an increase in number of ramified microglia in the parietal, entorhinal and frontal cortices, septum, basal ganglia, thalamus, medulla oblongata and internal capsule in the stressed pups as compared to controls, but also there was a reduction of amoeboid microglia and the total number of microglia in the corpus callosum. By postnatal day 10, there were no differences in the morphologic type or the distribution of microglia between the prenatal stress and control groups, except in the corpus callosum; where prenatal stress decreased the number of ramified microglia. The stress procedure was effective in producing plasma rise in corticosterone levels of pregnant rats at embryonic day 20 when compared to same age controls. Prenatal stress reduced the number of immature microglia and promoted an accelerated microglial differentiation into a ramified form. These findings may be related to an increase in plasma corticosterone in the pregnant dam. PMID:19756668
Self-affirmation alters the brain's response to health messages and subsequent behavior change.
Falk, Emily B; O'Donnell, Matthew Brook; Cascio, Christopher N; Tinney, Francis; Kang, Yoona; Lieberman, Matthew D; Taylor, Shelley E; An, Lawrence; Resnicow, Kenneth; Strecher, Victor J
Health communications can be an effective way to increase positive health behaviors and decrease negative health behaviors; however, those at highest risk are often most defensive and least open to such messages. For example, increasing physical activity among sedentary individuals affects a wide range of important mental and physical health outcomes, but has proven a challenging task. Affirming core values (i.e., self-affirmation) before message exposure is a psychological technique that can increase the effectiveness of a wide range of interventions in health and other domains; however, the neural mechanisms of affirmation's effects have not been studied. We used functional magnetic resonance imaging (fMRI) to examine neural processes associated with affirmation effects during exposure to potentially threatening health messages. We focused on an a priori defined region of interest (ROI) in ventromedial prefrontal cortex (VMPFC), a brain region selected for its association with self-related processing and positive valuation. Consistent with our hypotheses, those in the self-affirmation condition produced more activity in VMPFC during exposure to health messages and went on to increase their objectively measured activity levels more. These findings suggest that affirmation of core values may exert its effects by allowing at-risk individuals to see the self-relevance and value in otherwise-threatening messages. PMID:25646442
Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Alter the Gut-Brain Communication
Ballsmider, L. A.; Vaughn, A. C.; David, M.; Hajnal, A.; Di Lorenzo, P. M.; Czaja, K.
This study investigated the anatomical integrity of vagal innervation of the gastrointestinal tract following vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) operations. The retrograde tracer fast blue (FB) was injected into the stomach to label vagal neurons originating from nodose ganglion (NG) and dorsal motor nucleus of the vagus (DMV). Microglia activation was determined by quantifying changes in the fluorescent staining of hindbrain sections against an ionizing calcium adapter binding molecule 1 (Iba1). Reorganization of vagal afferents in the hindbrain was studied by fluorescent staining against isolectin 4 (IB4). The density of Iba1- and IB4-immunoreactivity was analyzed using Nikon Elements software. There was no difference in the number of FB-labeled neurons located in NG and DMV between VSG and VSG-sham rats. RYGB, but not RYGB-sham rats, showed a dramatic reduction in number of FB-labeled neurons located in the NG and DMV. VSG increased, while the RYGB operation decreased, the density of vagal afferents in the nucleus tractus solitarius (NTS). The RYGB operation, but not the VSG procedure, significantly activated microglia in the NTS and DMV. Results of this study show that the RYGB, but not the VSG procedure, triggers microglia activation in vagal structures and remodels gut-brain communication. PMID:25722893
Organic matter alteration at active and relict sedimentary oxidation fronts
Cowie, G.L.; Calvert, S.E. (Univ. of British Columbia, Vancouver (Canada)); Hedges, J.I. (Univ. of Washington, Seattle, WA (United States)) (and others)
Sedimentary oxidation fronts, generated by downward diffusion of O[sub 2] into previously reducing sediments, provide an opportunity to study the effects of O[sub 2] exposure on organic matter preservation, where other factors are invariant. Oxidation fronts have now been identified in a number of environments, including turbidities found on the Madeira abyssal plain (NE Atlantic) and in sapropels from the Mediterranean. A multifaceted study is being carried out on a series of relict fronts in turbidities of varied origin and composition, recovered from the Madeira abyssal plain on ODP Leg 157. A similar study is being made on an active front in the most recent, S1 sapropel, from the central Mediterranean. In both cases, the relatively organic-rich turbidities and sapropels are intercalated with typical, organic-poor pelagic marts. Analyses include major and minor inorganic elements, stable and N isotopes, palynomorphs, surface areas and a comprehensive suite of biochemicals. Although the extent of alteration varies, striking changes in organic content and composition occur across many of the oxidation fronts, and the oxidized horizons resemble the interclated marls. A common trend is that organic C contents drop from [open quotes]monolayer equivalent[close quotes] sorptive loadings in the unoxidized horizons (typical of continental mar in sediments) to submonolayer loadings, typical of the pelagic marls. Shifts are also observed in redox-sensitive trace metals and in stable C and N isotopic compositions, although the patterns and extent are not uniform. The results clearly indicate that in these pelagic settings, where O[sub 2] exposure is typically long, organic material deposited and then preserved for extended periods under anomalous reducing conditions, can be extensively altered on relatively short-term exposure to O[sub 2] Implications of these findings will be discussed.
Organic matter alteration at active and relict sedimentary oxidation fronts
Cowie, G.L.; Calvert, S.E. [Univ. of British Columbia, Vancouver (Canada); Hedges, J.I. [Univ. of Washington, Seattle, WA (United States)] [and others
Sedimentary oxidation fronts, generated by downward diffusion of O{sub 2} into previously reducing sediments, provide an opportunity to study the effects of O{sub 2} exposure on organic matter preservation, where other factors are invariant. Oxidation fronts have now been identified in a number of environments, including turbidities found on the Madeira abyssal plain (NE Atlantic) and in sapropels from the Mediterranean. A multifaceted study is being carried out on a series of relict fronts in turbidities of varied origin and composition, recovered from the Madeira abyssal plain on ODP Leg 157. A similar study is being made on an active front in the most recent, S1 sapropel, from the central Mediterranean. In both cases, the relatively organic-rich turbidities and sapropels are intercalated with typical, organic-poor pelagic marts. Analyses include major and minor inorganic elements, stable and N isotopes, palynomorphs, surface areas and a comprehensive suite of biochemicals. Although the extent of alteration varies, striking changes in organic content and composition occur across many of the oxidation fronts, and the oxidized horizons resemble the interclated marls. A common trend is that organic C contents drop from {open_quotes}monolayer equivalent{close_quotes} sorptive loadings in the unoxidized horizons (typical of continental mar in sediments) to submonolayer loadings, typical of the pelagic marls. Shifts are also observed in redox-sensitive trace metals and in stable C and N isotopic compositions, although the patterns and extent are not uniform. The results clearly indicate that in these pelagic settings, where O{sub 2} exposure is typically long, organic material deposited and then preserved for extended periods under anomalous reducing conditions, can be extensively altered on relatively short-term exposure to O{sub 2} Implications of these findings will be discussed.
Shiga Toxin 1 Induces on Lipopolysaccharide-Treated Astrocytes the Release of Tumor Necrosis Factor-alpha that Alter Brain-Like Endothelium Integrity
Landoni, Verónica I.; Schierloh, Pablo; de Campos Nebel, Marcelo; Fernández, Gabriela C.; Calatayud, Cecilia; Lapponi, María J.; Isturiz, Martín A.
The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and renal dysfunction. The typical form of HUS is generally associated with infections by Gram-negative Shiga toxin (Stx)-producing Escherichia coli (STEC). Endothelial dysfunction induced by Stx is central, but bacterial lipopolysaccharide (LPS) and neutrophils (PMN) contribute to the pathophysiology. Although renal failure is characteristic of this syndrome, neurological complications occur in severe cases and is usually associated with death. Impaired blood-brain barrier (BBB) is associated with damage to cerebral endothelial cells (ECs) that comprise the BBB. Astrocytes (ASTs) are inflammatory cells in the brain and determine the BBB function. ASTs are in close proximity to ECs, hence the study of the effects of Stx1 and LPS on ASTs, and the influence of their response on ECs is essential. We have previously demonstrated that Stx1 and LPS induced activation of rat ASTs and the release of inflammatory factors such as TNF-?, nitric oxide and chemokines. Here, we demonstrate that rat ASTs-derived factors alter permeability of ECs with brain properties (HUVECd); suggesting that functional properties of BBB could also be affected. Additionally, these factors activate HUVECd and render them into a proagregant state promoting PMN and platelets adhesion. Moreover, these effects were dependent on ASTs secreted-TNF-?. Stx1 and LPS-induced ASTs response could influence brain ECs integrity and BBB function once Stx and factors associated to the STEC infection reach the brain parenchyma and therefore contribute to the development of the neuropathology observed in HUS. PMID:22479186
In vivo recordings of brain activity using organic transistors
Khodagholy, Dion; Doublet, Thomas; Quilichini, Pascale; Gurfinkel, Moshe; Leleux, Pierre; Ghestem, Antoine; Ismailova, Esma; Hervé, Thierry; Sanaur, Sébastien; Bernard, Christophe; Malliaras, George G.
In vivo electrophysiological recordings of neuronal circuits are necessary for diagnostic purposes and for brain-machine interfaces. Organic electronic devices constitute a promising candidate because of their mechanical flexibility and biocompatibility. Here we demonstrate the engineering of an organic electrochemical transistor embedded in an ultrathin organic film designed to record electrophysiological signals on the surface of the brain. The device, tested in vivo on epileptiform discharges, displayed superior signal-to-noise ratio due to local amplification compared with surface electrodes. The organic transistor was able to record on the surface low-amplitude brain activities, which were poorly resolved with surface electrodes. This study introduces a new class of biocompatible, highly flexible devices for recording brain activity with superior signal-to-noise ratio that hold great promise for medical applications. PMID:23481383
Decoding mental states from brain activity in humans.
Haynes, John-Dylan; Rees, Geraint
Recent advances in human neuroimaging have shown that it is possible to accurately decode a person's conscious experience based only on non-invasive measurements of their brain activity. Such 'brain reading' has mostly been studied in the domain of visual perception, where it helps reveal the way in which individual experiences are encoded in the human brain. The same approach can also be extended to other types of mental state, such as covert attitudes and lie detection. Such applications raise important ethical issues concerning the privacy of personal thought. PMID:16791142
Brain modularity controls the critical behavior of spontaneous activity.
Russo, R; Herrmann, H J; de Arcangelis, L
The human brain exhibits a complex structure made of scale-free highly connected modules loosely interconnected by weaker links to form a small-world network. These features appear in healthy patients whereas neurological diseases often modify this structure. An important open question concerns the role of brain modularity in sustaining the critical behaviour of spontaneous activity. Here we analyse the neuronal activity of a model, successful in reproducing on non-modular networks the scaling behaviour observed in experimental data, on a modular network implementing the main statistical features measured in human brain. We show that on a modular network, regardless the strength of the synaptic connections or the modular size and number, activity is never fully scale-free. Neuronal avalanches can invade different modules which results in an activity depression, hindering further avalanche propagation. Critical behaviour is solely recovered if inter-module connections are added, modifying the modular into a more random structure. PMID:24621482
Brain modularity controls the critical behavior of spontaneous activity
NASA Astrophysics Data System (ADS)
Russo, R.; Herrmann, H. J.; de Arcangelis, L.
The human brain exhibits a complex structure made of scale-free highly connected modules loosely interconnected by weaker links to form a small-world network. These features appear in healthy patients whereas neurological diseases often modify this structure. An important open question concerns the role of brain modularity in sustaining the critical behaviour of spontaneous activity. Here we analyse the neuronal activity of a model, successful in reproducing on non-modular networks the scaling behaviour observed in experimental data, on a modular network implementing the main statistical features measured in human brain. We show that on a modular network, regardless the strength of the synaptic connections or the modular size and number, activity is never fully scale-free. Neuronal avalanches can invade different modules which results in an activity depression, hindering further avalanche propagation. Critical behaviour is solely recovered if inter-module connections are added, modifying the modular into a more random structure.
Mapping human brain activity in vivo.
Mazziotta, J C
A wide range of structural and functional techniques now exists to map the human brain in health and disease. These approaches span the gamut from external tomographic imaging devices (positron-emission tomography, single photon-emission computed tomography, magnetic resonance imaging, computed tomography), to surface detectors (electroencephalography, magnetoencephalography, transcranial magnetic stimulation), to measurements made directly on the brain's surface or beneath it (intrinsic signal imaging, electrocorticography). The noninvasive methods have been combined to provide unique and previously unavailable insights into the macroscopic organization of the functional neuroanatomy of human vision, sensation, hearing, movement, language, learning, and memory. All methods have been applied to patients with neurologic, neurosurgical, and psychiatric disease and have provided a rapidly expanding knowledge of the pathophysiology of diseases such as epilepsy, cerebrovascular disease, neoplasms, neurodegenerative diseases, mental illness, and addiction states. In addition, these new methods have become a mainstay of preoperative surgical planning and the monitoring of pharmacologic or surgical (transplantation) interventions. Most recently, the ability to observe the reorganization of the human nervous system after acute injury, such as occurs with cerebral infarction or head trauma, or in the course of a progressive degenerative process such as Alzheimer's or Parkinson's disease, may provide new insights and methods in the rapidly expanding field of neurorehabilitation. Our newfound ability to generate maps and databases of human brain development, maturation, skill acquisition, aging, and disease states is both an exciting and formidable task. PMID:7975566
Several reports have indicated that polychlorinated biphenyls (PCB) altered development of biogenic amine systems in the brain, impaired behavioral performances and disrupted maturation of the thyroid axis. The current study examines whether these developmental effects of PCB ar...
Progressive Brain Damage, Synaptic Reorganization and NMDA Activation in a Model of Epileptogenic Cortical Dysplasia
Colciaghi, Francesca; Finardi, Adele; Nobili, Paola; Locatelli, Denise; Spigolon, Giada; Battaglia, Giorgio Stefano
Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE) and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i) is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii) changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii) induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv) activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity. PMID:24587109
Abnormal baseline brain activity in patients with pulsatile tinnitus: a resting-state FMRI study.
Han, Lv; Zhaohui, Liu; Fei, Yan; Ting, Li; Pengfei, Zhao; Wang, Du; Cheng, Dong; Pengde, Guo; Xiaoyi, Han; Xiao, Wang; Rui, Li; Zhenchang, Wang
Numerous investigations studying the brain functional activity of the tinnitus patients have indicated that neurological changes are important findings of this kind of disease. However, the pulsatile tinnitus (PT) patients were excluded in previous studies because of the totally different mechanisms of the two subtype tinnitus. The aim of this study is to investigate whether altered baseline brain activity presents in patients with PT using resting-state functional magnetic resonance imaging (rs-fMRI) technique. The present study used unilateral PT patients (n = 42) and age-, sex-, and education-matched normal control subjects (n = 42) to investigate the changes in structural and amplitude of low-frequency (ALFF) of the brain. Also, we analyzed the relationships between these changes with clinical data of the PT patients. Compared with normal controls, PT patients did not show any structural changes. PT patients showed significant increased ALFF in the bilateral precuneus, and bilateral inferior frontal gyrus (IFG) and decreased ALFF in multiple occipital areas. Moreover, the increased THI score and PT duration was correlated with increased ALFF in precuneus and bilateral IFG. The abnormalities of spontaneous brain activity reflected by ALFF measurements in the absence of structural changes may provide insights into the neural reorganization in PT patients. PMID:24872895
Cannabinoid-induced alterations in brain disposition of drugs of abuse.
Reid, M J; Bornheim, L M
Marijuana contains a complex mixture of compounds including tetrahydrocannabinol (THC), the major psychoactive constituent, and cannabidiol (CBD), a nonpsychoactive constituent. We have shown previously that CBD pretreatment of mice increases brain levels of THC and have now further characterized this effect and determined whether the brain pharmacokinetics of other drugs are also affected. CBD pretreatment of mice (30-60 min) increased brain levels of THC nearly 3-fold, whereas CBD co-administration did not. Because marijuana is often consumed with other drugs, the influence of cannabinoids on the brain levels of several other drugs of abuse was also determined. CBD pretreatment of mice increased brain levels (2- to 4-fold) of subsequently administered cocaine as well as phencyclidine (PCP). Although CBD pretreatment increased blood and brain levels of cocaine comparably, blood levels of PCP were only modestly elevated (up to 50%). Behavioral tests indicated that the CBD-mediated increases in the brain levels of THC, cocaine, and PCP correlated with increased pharmacological responses. Pretreatment with THC instead of CBD could similarly increase brain levels of cocaine, PCP, and CBD, although with a lower potency than CBD. On the other hand, pretreatment of mice with CBD had no effect on the brain levels of several other drugs of abuse including morphine, methadone, or methylenedioxyphenyl-methamphetamine. These findings demonstrate that cannabinoids can increase the brain concentrations and pharmacological actions of several other drugs of abuse, thereby providing a biochemical basis for the common practice of using marijuana concurrently with such drugs. PMID:11331071
Synchronous brain activity across individuals underlies shared psychological perspectives
Lahnakoski, Juha M.; Glerean, Enrico; Jääskeläinen, Iiro P.; Hyönä, Jukka; Hari, Riitta; Sams, Mikko; Nummenmaa, Lauri
For successful communication, we need to understand the external world consistently with others. This task requires sufficiently similar cognitive schemas or psychological perspectives that act as filters to guide the selection, interpretation and storage of sensory information, perceptual objects and events. Here we show that when individuals adopt a similar psychological perspective during natural viewing, their brain activity becomes synchronized in specific brain regions. We measured brain activity with functional magnetic resonance imaging (fMRI) from 33 healthy participants who viewed a 10-min movie twice, assuming once a 'social' (detective) and once a 'non-social' (interior decorator) perspective to the movie events. Pearson's correlation coefficient was used to derive multisubject voxelwise similarity measures (inter-subject correlations; ISCs) of functional MRI data. We used k-nearest-neighbor and support vector machine classifiers as well as a Mantel test on the ISC matrices to reveal brain areas wherein ISC predicted the participants' current perspective. ISC was stronger in several brain regions—most robustly in the parahippocampal gyrus, posterior parietal cortex and lateral occipital cortex—when the participants viewed the movie with similar rather than different perspectives. Synchronization was not explained by differences in visual sampling of the movies, as estimated by eye gaze. We propose that synchronous brain activity across individuals adopting similar psychological perspectives could be an important neural mechanism supporting shared understanding of the environment. PMID:24936687
Synchronous brain activity across individuals underlies shared psychological perspectives.
Lahnakoski, Juha M; Glerean, Enrico; Jääskeläinen, Iiro P; Hyönä, Jukka; Hari, Riitta; Sams, Mikko; Nummenmaa, Lauri
For successful communication, we need to understand the external world consistently with others. This task requires sufficiently similar cognitive schemas or psychological perspectives that act as filters to guide the selection, interpretation and storage of sensory information, perceptual objects and events. Here we show that when individuals adopt a similar psychological perspective during natural viewing, their brain activity becomes synchronized in specific brain regions. We measured brain activity with functional magnetic resonance imaging (fMRI) from 33 healthy participants who viewed a 10-min movie twice, assuming once a 'social' (detective) and once a 'non-social' (interior decorator) perspective to the movie events. Pearson's correlation coefficient was used to derive multisubject voxelwise similarity measures (inter-subject correlations; ISCs) of functional MRI data. We used k-nearest-neighbor and support vector machine classifiers as well as a Mantel test on the ISC matrices to reveal brain areas wherein ISC predicted the participants' current perspective. ISC was stronger in several brain regions--most robustly in the parahippocampal gyrus, posterior parietal cortex and lateral occipital cortex--when the participants viewed the movie with similar rather than different perspectives. Synchronization was not explained by differences in visual sampling of the movies, as estimated by eye gaze. We propose that synchronous brain activity across individuals adopting similar psychological perspectives could be an important neural mechanism supporting shared understanding of the environment. PMID:24936687
Effect of acute exposure of triazophos on oxidative stress and histopathological alterations in liver, kidney and brain of Wistar rats.
Mohineesh; Raj, Jaya; Rajvanshi, A C; Dogra, T D; Raina, Anupuma
Acute dose of organophosphorus pesticide Triazophos (O,O-diethyl O-1-phenyl-1H-1,2,4-triazol-3-yl phosphorothioate; Tz) administered orally affects oxidative stress parameters and the histo-architecture of liver, kidney and brain tissues. The results indicate a dose dependent induction of oxidative stress as evident by increased malondialdehyde level and decreased antioxidant defense including glutathione and superoxide dismutase activity in rat liver, kidney and brain. AChE activity was found significantly decreased in the Tz treated groups as compared to the vehicle control (DMSO) group. Histopathological examination of liver, kidney and brain in Tz treated rats revealed medullary congestion and hydropic degeneration of hepatocytes in liver and medullary congestion in kidney. However, no significant histopathological changes were observed in brain tissues. PMID:25141545
Brain acetycholinesterase activity in botulism-intoxicated mallards
Rocke, T.E.; Samuel, M.D.
Brain acetylcholinesterase (AChE) activity in captive-reared mallards (Anas platyrhynchos) that died of botulism was compared with euthanized controls. AChE levels for both groups were within the range reported for normal mallards, and there was no significant difference in mean AChE activity between birds that ingested botulism toxin and died and those that did not.
Genetic variation in CNTNAP2 alters brain function during linguistic processing in healthy individuals.
Whalley, Heather C; O'Connell, Garret; Sussmann, Jessika E; Peel, Anna; Stanfield, Andrew C; Hayiou-Thomas, Marianna E; Johnstone, Eve C; Lawrie, Stephen M; McIntosh, Andrew M; Hall, Jeremy
Language impairments are a characteristic feature of autism and related autism spectrum disorders (ASDs). Autism is also highly heritable and one of the most promising candidate genes implicated in its pathogenesis is contactin-associated protein-like 2 (CNTNAP2), a gene also associated with language impairment. In the current study we investigated the functional effects of variants of CNTNAP2 associated with autism and language impairment (rs7794745 and rs2710102; presumed risk alleles T and C, respectively) in healthy individuals using functional magnetic resonance imaging (fMRI) during performance of a language task (n = 66). Against a background of normal performance and lack of behavioral abnormalities, healthy individuals with the putative risk allele versus those without demonstrated significant increases in activation in the right inferior frontal gyrus (Broca's area homologue) and right lateral temporal cortex. These findings demonstrate that risk associated variation in the CNTNAP2 gene impacts on brain activation in healthy non-autistic individuals during a language processing task providing evidence of the effect of genetic variation in CNTNAP2 on a core feature of ASDs. PMID:21987501
Expression of astrocytic genes coding for proteins implicated in neural excitation and brain edema is altered after acute liver failure.
Thumburu, Kiran K; Dhiman, Radha K; Vasishta, Rakesh K; Chakraborti, Anuradha; Butterworth, Roger F; Beauchesne, Elizabeth; Desjardins, Paul; Goyal, Sandeep; Sharma, Navneet; Duseja, Ajay; Chawla, Yogesh
In vitro and in vivo studies have suggested that reduced astrocytic uptake of neuronally released glutamate, alterations in expression of glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP-4) contribute to brain edema in acute liver failure (ALF). However, there is no evidence to date to suggest that these alterations occur in patients with ALF. We analyzed the mRNA expression of excitatory amino acid transporters (EAAT-1, EAAT-2), GFAP, and AQP-4 in the cerebral cortex obtained at autopsy from eight patients with ALF and from seven patients with no evidence of hepatic or neurological disorders by real-time PCR, and protein expression was assessed using immunoblotting and immunohistochemistry. We demonstrated a significant decrease in GFAP mRNA and protein levels in ALF patients compared to controls. While the loss of EAAT-2 protein in ALF samples was post-translational in nature, EAAT-1 protein remained within normal limits. Immunohistochemistry confirmed that, in all cases, the losses of EAAT-2 and GFAP were uniquely astrocytic in their localization. AQP-4 mRNA expression was significantly increased and its immunohistochemistry demonstrated increased AQP-4 immunoreactivity in the glial end-feet process surrounding the microvessels. These findings provide evidence of selective alterations in the expression of genes coding for key astrocytic proteins implicated in central nervous system (CNS) excitability and brain edema in human ALF. We investigated the gene expression of astrocytic proteins involved in astrocyte swelling causing brain edema in autopsied brain tissues of patients with acute liver failure. This study demonstrated loss of GFAP expression and up-regulation of AQP-4 protein expression leading to cerebral edema, and loss of EAAT-2 expression implicated in excitatory neurotransmission. These findings may provide new drug targets against CNS complications of acute liver failure. PMID:24164438
Altered expression of circadian clock gene, mPer1, in mouse brain and kidney under morphine dependence and withdrawal
Wang, Xiaojia; Wang, Yueqi; Xin, Haoyang; Liu, Yanyou; Wang, Yuhui; Zheng, Hang; Jiang, Zhou; Wan, Chaomin; Wang, Zhengrong; Ding, Jian M
Every physiological function in the human body exhibits some form of circadian rhythmicity. Under pathological conditions, however, circadian rhythmicity may be dusrupted. Patients infected with HIV or addicted to drugs of abuse often suffer from sleep disorders and altered circadian rhythms. Early studies in Drosophila suggested that drug seeking behavior might be related to the expression of certain circadian clock genes. Our previous research showed that conditioned place preference with morphine treatment was altered in mice lacking the Period-1 (mPer1) circadian clock gene. Thus, we sought to investigate whether morphine treatment could alter the expression of mPer1, especially in brain regions outside the SCN and in peripheral tissues. Our results using Western blot analysis showed that the mPER1 immunoreactivity exhibited a strong circadian rhythm in the brains of the control (Con), morphine-dependent (MD), and morphine-withdrawal (MW) mice. However, the phase of the circadian rhythm of mPER1 expression in the brains of MD mice significantly differed from that of the Con mice (p < 0.05). In contrast to mPER1 expression in the brain, the circadian rhythm of mPER1 immunoreactivity in the kidneys was abolished after morphine administration, whereas the Con mice maintained robust circadian rhythmicity of mPER1 in the kidney. Therefore, the effect of morphine on the circadian clock gene mPer1 may vary among different organs, resulting in desynchronization of circadian function between the SCN and peripheral organs. PMID:16925815
Uncovering Intrinsic Modular Organization of Spontaneous Brain Activity in Humans
He, Yong; Wang, Jinhui; Wang, Liang; Chen, Zhang J.; Yan, Chaogan; Yang, Hong; Tang, Hehan; Zhu, Chaozhe; Gong, Qiyong; Zang, Yufeng; Evans, Alan C.
The characterization of topological architecture of complex brain networks is one of the most challenging issues in neuroscience. Slow (<0.1 Hz), spontaneous fluctuations of the blood oxygen level dependent (BOLD) signal in functional magnetic resonance imaging are thought to be potentially important for the reflection of spontaneous neuronal activity. Many studies have shown that these fluctuations are highly coherent within anatomically or functionally linked areas of the brain. However, the underlying topological mechanisms responsible for these coherent intrinsic or spontaneous fluctuations are still poorly understood. Here, we apply modern network analysis techniques to investigate how spontaneous neuronal activities in the human brain derived from the resting-state BOLD signals are topologically organized at both the temporal and spatial scales. We first show that the spontaneous brain functional networks have an intrinsically cohesive modular structure in which the connections between regions are much denser within modules than between them. These identified modules are found to be closely associated with several well known functionally interconnected subsystems such as the somatosensory/motor, auditory, attention, visual, subcortical, and the "default" system. Specifically, we demonstrate that the module-specific topological features can not be captured by means of computing the corresponding global network parameters, suggesting a unique organization within each module. Finally, we identify several pivotal network connectors and paths (predominantly associated with the association and limbic/paralimbic cortex regions) that are vital for the global coordination of information flow over the whole network, and we find that their lesions (deletions) critically affect the stability and robustness of the brain functional system. Together, our results demonstrate the highly organized modular architecture and associated topological properties in the temporal and spatial brain functional networks of the human brain that underlie spontaneous neuronal dynamics, which provides important implications for our understanding of how intrinsically coherent spontaneous brain activity has evolved into an optimal neuronal architecture to support global computation and information integration in the absence of specific stimuli or behaviors. PMID:19381298
Intracellular alterations of the creatine kinase isoforms in brains of schizophrenic patients
Tatyana P. Klushnik; Alexander Ya. Spunde; Alexander G. Yakovlev; Zaza A. Khuchua; Valdur A. Saks; Marat E. Vartanyan
Postmortem brain tissues of schizophrenic patients were found to contain 5–10 times less water-soluble creatine kinase (BB\\u000a CK) and 1.5–3 times less mitochondrial creatine kinase as compared to control. The major part of BB CK in schizophrenic brain\\u000a tissues, contrary to control, was found to be insoluble in water (particulate form of BB CK) and could be extracted from brain
Transient activation of dopaminergic neurons during development modulates visual responsiveness, locomotion and brain activity in a dopamine ontogeny model of schizophrenia.
Calcagno, B; Eyles, D; van Alphen, B; van Swinderen, B
It has been observed that certain developmental environmental risk factors for schizophrenia when modeled in rodents alter the trajectory of dopaminergic development, leading to persistent behavioural changes in adults. This has recently been articulated as the "dopamine ontogeny hypothesis of schizophrenia". To test one aspect of this hypothesis, namely that transient dopaminergic effects during development modulate attention-like behavior and arousal in adults, we turned to a small-brain model, Drosophila melanogaster. By applying genetic tools allowing transient activation or silencing of dopaminergic neurons in the fly brain, we investigated whether a critical window exists during development when altered dopamine (DA) activity levels could lead to impairments in arousal states in adult animals. We found that increased activity in dopaminergic neurons in later stages of development significantly increased visual responsiveness and locomotion, especially in adult males. This misallocation of visual salience and hyperactivity mimicked the effect of acute methamphetamine feeding to adult flies, suggesting up-regulated DA signaling could result from developmental manipulations. Finally, brain recordings revealed significantly reduced gamma-band activity in adult animals exposed to the transient developmental insult. Together, these data support the idea that transient alterations in DA signaling during development can permanently alter behavior in adults, and that a reductionist model such as Drosophila can be used to investigate potential mechanisms underlying complex cognitive disorders such as schizophrenia. PMID:23299394
Can human activities alter the drowning fate of barrier islands?
NASA Astrophysics Data System (ADS)
Lorenzo-Trueba, J.; Ashton, A. D.; Jin, D.; Hoagland, P.; Kite-Powell, H.
Low-lying coastal barriers face an uncertain future over the coming century and beyond as sea levels rise, with many projections suggesting end-of-century rates of sea-level rise as high or higher than 1 cm/yr. Geologically, such rates of sea-level rise have been experienced several thousand years ago and we can use our understanding of geological processes and sedimentary evidence to help unravel the dynamics of natural barriers experiencing sea-level rise. Along many modern coastal barriers, however, anthropic change, such as beach nourishment, dune construction, and emplacement of hard structures, plays a dominant role in coastline dynamics. A fundamental question to be addressed is whether human activities intended to preserve infrastructure and beach recreation may make wholesale collapse, or 'drowning,' of barrier systems more likely. Here we present a numerical modeling tool that couples natural processes and the human responses to these changes (and the subsequent of human responses on natural processes). Recent theoretical model development suggests that barriers are intrinsically morphodynamic features, responding to sea-level rise in complex ways through the interactions of marine processes and barrier overwash. Undeveloped coastal barriers would therefore respond to an accelerated sea-level rise in complex, less predictable manners than suggested by existing long-term models. We have developed a model that examines non-equilibrium cross-shore evolution of barrier systems at decadal to centennial temporal scales, focusing on the interactions between processes of shoreface evolution and overwash deposition. Model responses demonstrate two means of barrier collapse during sea-level rise: 'height drowning', which occurs when overwash fluxes are insufficient to maintain the landward migration rate required to keep in pace with sea-level rise, and 'width drowning', which occurs when the shoreface response is insufficient to maintain the barrier geometry during landward migration. The model also demonstrates the potential for discontinuous shoreline retreat, with alternating periods of barrier stability and rapid migration, even for constant rates of sea-level rise. Anthropic activities can strongly interact with these behaviors. In particular, considering only cross-shore processes, beach nourishment activities widen the beach and can affect shoreface fluxes, and dune building, which curtails the overwash process, can potentially enhance barrier drowning by reducing overwash fluxes. Furthermore, coastal protection activities of adjacent communities or even individual property holders can be uncoordinated or coordinated, with their effects coupled along the coast through coastal reorientation and gradients in alongshore sediment transport. In the coordinated framework, owners act in concert to alter the barrier based upon community benefits, whereas in the non-coordinated framework owners alter only their own property. Another important role in management is the perception of future sea-level-rise-associated losses—communities manage their coast differently depending on their adopted forecast for sea-level rise. We find that coordinated behavior coupled with natural processes can substantially affect the drowning scenarios from the individual decision-making process.
Suramin Increased Telomerase Activity in the C6 Glioma/Wistar Experimental Brain Tumor Model
Ergüven, Mine; Bilir, Ayhan; Altug, Tuncay; Aktar, Fadime; Akev, Nuriye
Glioblastoma multiforme (GBM) is the most treatment-resistant glioma variant. Significant roles for telomerase in etiology, recurrence and drug resistance of GBM have been highlighted. Suramin (Bayer, Leverkusen, Germany) is an antineoplastic agent that affects many cellular mechanisms including growth factor, purinergic receptor, cytokine and key cellular enzymes signaling. The aim of this study was to investigate whether suramin, 40 mg/kg, i.p., inhibits telomerase activity in a subcutaneous C6 glioma/Wistar experimental brain tumor model using PCR based telomeric repeat amplification assay. In comparison to the control group, suramin increased tumor volume and telomerase activity. We also used transmission electron microscopy to evaluate the alterations of cell morphology. Apoptosis was seen markedly in electron micrographs of the control group and anti-apoptotic activity of telomerase was verified in the electron micrographs of suramin-applied group. The in vitro inhibitory effects of suramin on telomerase activity in several cell lines except for brain tumors have been reported. Contrary to in vitro reports, our results were the first to demonstrate that suramin increased telomerase activity in a C6 glioma/Wistar experimental brain tumor. Large numbers of drugs exhibited apparent hormetic effects on cultured cancer cells and in vivo cancer growth. Several drug examples for their hormetic effects in vivo were listed as resveratrol, suramin, and tamoxifen. The action of suramin in the present study could be evaluated as one of the hormetic examples of suramin in vivo. PMID:23675031
Suramin increased telomerase activity in the c6 glioma/wistar experimental brain tumor model.
Ergüven, Mine; Bilir, Ayhan; Altug, Tuncay; Aktar, Fadime; Akev, Nuriye
Glioblastoma multiforme (GBM) is the most treatment-resistant glioma variant. Significant roles for telomerase in etiology, recurrence and drug resistance of GBM have been highlighted. Suramin (Bayer, Leverkusen, Germany) is an antineoplastic agent that affects many cellular mechanisms including growth factor, purinergic receptor, cytokine and key cellular enzymes signaling. The aim of this study was to investigate whether suramin, 40 mg/kg, i.p., inhibits telomerase activity in a subcutaneous C6 glioma/Wistar experimental brain tumor model using PCR based telomeric repeat amplification assay. In comparison to the control group, suramin increased tumor volume and telomerase activity. We also used transmission electron microscopy to evaluate the alterations of cell morphology. Apoptosis was seen markedly in electron micrographs of the control group and anti-apoptotic activity of telomerase was verified in the electron micrographs of suramin-applied group. The in vitro inhibitory effects of suramin on telomerase activity in several cell lines except for brain tumors have been reported. Contrary to in vitro reports, our results were the first to demonstrate that suramin increased telomerase activity in a C6 glioma/Wistar experimental brain tumor. Large numbers of drugs exhibited apparent hormetic effects on cultured cancer cells and in vivo cancer growth. Several drug examples for their hormetic effects in vivo were listed as resveratrol, suramin, and tamoxifen. The action of suramin in the present study could be evaluated as one of the hormetic examples of suramin in vivo. PMID:23675031
Prefrontal Transcranial Direct Current Stimulation Alters Activation and Connectivity in Cortical and Subcortical Reward Systems: A tDCS-fMRI Study
Weber, Matthew J.; Messing, Samuel B.; Rao, Hengyi; Detre, John A.; Thompson-Schill, Sharon L.
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique used both experimentally and therapeutically to modulate regional brain function. However, few studies have directly measured the aftereffects of tDCS on brain activity or examined changes in task-related brain activity consequent to prefrontal tDCS. To investigate the neural effects of tDCS, we collected fMRI data from 22 human subjects, both at rest and while performing the Balloon Analog Risk Task (BART), before and after true or sham transcranial direct current stimulation. TDCS decreased resting blood perfusion in orbitofrontal cortex and the right caudate and increased task-related activity in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in response to losses but not wins or increasing risk. Network analysis showed that whole-brain connectivity of the right ACC correlated positively with the number of pumps subjects were willing to make on the BART, and that tDCS reduced connectivity between the right ACC and the rest of the brain. Whole-brain connectivity of the right DLPFC also correlated negatively with pumps on the BART, as prior literature would suggest. Our results suggest that tDCS can alter activation and connectivity in regions distal to the electrodes. PMID:24453107
Mediating effects of aryl-hydrocarbon receptor and RhoA in altering brain vascular integrity: the therapeutic potential of statins.
Chang, Chih-Cheng; Lee, Pei-Shan; Chou, Ying; Hwang, Ling-Ling; Juan, Shu-Hui
We have demonstrated previously that focal adhesion kinase (FAK)/RhoA alteration by the aryl-hydrocarbon receptor (AhR) agonist 3-methylcholanthrene (3MC) is involved in the antimigratory effects of 3MC in human umbilical vascular endothelial cells. Here, we identified that signaling properties and molecular mechanisms of RhoA/?-catenin were both implicated in alterations to blood-brain barrier integrity. The mechanisms of action were the down-regulation of integrin, the extracellular matrix, and adherens junction stability. PTEN phosphorylation by 3MC-mediated AhR/RhoA activation increased the proteasomal degradation of ?-catenin through PKC?/pGSK3?-mediated ?-catenin phosphorylation; the crucial roles of AhR/RhoA in this process were verified by using gain- or loss-of-function experiments. The decrease in ?-catenin led to decreased expression of fibronectin and ?5?1 integrin. Additionally, protein interactions among FAK, VE-cadherin, vinculin, and ?-actin were simultaneously decreased, resulting in adherens junction instability. Novel functional TCF/LEF1 binding sites in the promoter regions of fibronectin and ?5/?1 integrin were identified by electrophoretic mobility shift and chromatin immunoprecipitation assays. The results indicate that the binding activities of ?-catenin decreased in mouse cerebrovascular endothelial cells treated with 3MC. In addition, simvastatin and pravastatin treatment reversed 3MC-mediated alterations in mouse cerebrovascular endothelial cells by RhoA inactivation, and the in vitro findings were substantiated by an in vivo blood-brain barrier assay. Thus, endothelial barrier dysfunction due to 3MC occurs through AhR/RhoA-mediated ?-catenin down-regulation, which is reversed by simvastatin treatment in vivo. PMID:22720799
Brain feminization requires active repression of masculinization via DNA methylation.
Nugent, Bridget M; Wright, Christopher L; Shetty, Amol C; Hodes, Georgia E; Lenz, Kathryn M; Mahurkar, Anup; Russo, Scott J; Devine, Scott E; McCarthy, Margaret M
The developing mammalian brain is destined for a female phenotype unless exposed to gonadal hormones during a perinatal sensitive period. It has been assumed that the undifferentiated brain is masculinized by direct induction of transcription by ligand-activated nuclear steroid receptors. We found that a primary effect of gonadal steroids in the highly sexually dimorphic preoptic area (POA) is to reduce activity of DNA methyltransferase (Dnmt) enzymes, thereby decreasing DNA methylation and releasing masculinizing genes from epigenetic repression. Pharmacological inhibition of Dnmts mimicked gonadal steroids, resulting in masculinized neuronal markers and male sexual behavior in female rats. Conditional knockout of the de novo Dnmt isoform, Dnmt3a, also masculinized sexual behavior in female mice. RNA sequencing revealed gene and isoform variants modulated by methylation that may underlie the divergent reproductive behaviors of males versus females. Our data show that brain feminization is maintained by the active suppression of masculinization via DNA methylation. PMID:25821913
Alterations of social interaction through genetic and environmental manipulation of the 22q11.2 gene Sept5 in the mouse brain
Harper, Kathryn M.; Hiramoto, Takeshi; Tanigaki, Kenji; Kang, Gina; Suzuki, Go; Trimble, William; Hiroi, Noboru
Social behavior dysfunction is a symptomatic element of schizophrenia and autism spectrum disorder (ASD). Although altered activities in numerous brain regions are associated with defective social cognition and perception, the causative relationship between these altered activities and social cognition and perception—and their genetic underpinnings—are not known in humans. To address these issues, we took advantage of the link between hemizygous deletion of human chromosome 22q11.2 and high rates of social behavior dysfunction, schizophrenia and ASD. We genetically manipulated Sept5, a 22q11.2 gene, and evaluated its role in social interaction in mice. Sept5 deficiency, against a high degree of homogeneity in a congenic genetic background, selectively impaired active affiliative social interaction in mice. Conversely, virally guided overexpression of Sept5 in the hippocampus or, to a lesser extent, the amygdala elevated levels of active affiliative social interaction in C57BL/6J mice. Congenic knockout mice and mice overexpressing Sept5 in the hippocampus or amygdala were indistinguishable from control mice in novelty and olfactory responses, anxiety or motor activity. Moreover, post-weaning individual housing, an environmental condition designed to reduce stress in male mice, selectively raised levels of Sept5 protein in the amygdala and increased active affiliative social interaction in C57BL/6J mice. These findings identify this 22q11.2 gene in the hippocampus and amygdala as a determinant of social interaction and suggest that defective social interaction seen in 22q11.2-associated schizophrenia and ASD can be genetically and environmentally modified by altering this 22q11.2 gene. PMID:22589251
Alterations in Phosphorylated CREB Expression in Different Brain Regions following Short- and Long-Term Morphine Exposure: Relationship to Food Intake
Ren, Xiuhai; Lutfy, Kabirullah; Ferrini, Monica G.; Lee, Martin L.; Liu, Yanjun; Friedman, Theodore C.
Background. Activation of the cyclic adenosine monophosphate (cAMP)/phosphorylated CREB (P-CREB) system in different brain regions has been implicated in mediating opioid tolerance and dependence, while alteration of this system in the lateral hypothalamus (LH) has been suggested to have a role in food intake and body weight. Methods. Given that opioids regulate food intake, we measured P-CREB in different brain regions in mice exposed to morphine treatments designed to induce different degrees of tolerance and dependence. Results. We found that a single morphine injection or daily morphine injections for 8 days did not influence P-CREB levels, while the escalating dose of morphine regimen raised P-CREB levels only in the ventral tegmental area (VTA). Chronic morphine pellet implantation for 7 days raised P-CREB levels in the LH, VTA, and dorsomedial nucleus of the hypothalamus (DM) but not in the nucleus accumbens and amygdala. Increased P-CREB levels in LH, VTA, and DM following 7-day treatment with morphine pellets and increased P-CREB levels in the VTA following escalating doses of morphine were associated with decreased food intake and body weight. Conclusion. The morphine regulation of P-CREB may explain some of the physiological sequelae of opioid exposure including altered food intake and body weight. PMID:24073333
Altered microRNA expression profiles in post-mortem brain samples from individuals with schizophrenia and bipolar disorder
Moreau, Michael P.; Bruse, Shannon E.; David-Rus, Richard; Buyske, Steven; Brzustowicz, Linda M.
Background MicroRNAs (miRNAs) are potent regulators of gene expression with proposed roles in brain development and function. We hypothesized that miRNA expression profiles are altered in individuals with severe psychiatric disorders. Methods Using real-time quantitative PCR, we compared the expression of 435 miRNAs and 18 snoRNAs in post-mortem brain tissue samples from individuals with schizophrenia, individuals with bipolar disorder, and psychiatrically healthy control subjects (n = 35 each group). Detailed demographic data, sample selection and storage conditions, and drug and substance exposure histories were available for all subjects. Bayesian model averaging was used to simultaneously assess the impact of these covariates as well as the psychiatric phenotype on miRNA expression profiles. Results Of the variables considered, sample storage time, brain pH, alcohol at time of death, and post-mortem interval were found to affect the greatest proportion of miRNAs. 19% of miRNAs analyzed exhibited positive evidence of altered expression due to a diagnosis of schizophrenia or bipolar disorder. Both conditions were associated with reduced miRNA expression levels, with a much more pronounced effect observed for bipolar disorder. Conclusions This study suggests that modest under-expression of several miRNAs may be involved in the complex pathogenesis of major psychosis. PMID:21183010
Maternal protein restriction early in rat pregnancy alters brain development in the progeny
Pierre Gressens; Séverin M Muaku; Leslie Besse; Elise Nsegbe; Jorge Gallego; Bertrand Delpech; Claude Gaultier; Philippe Evrard; Jean-Marie Ketelslegers; Dominique Maiter
We assessed the effects of a dietary protein restriction (5% vs. 20% casein in diet) initiated at conception and imposed during the first 2 weeks of rat gestation on postnatal brain development. At the end of the malnutrition period, protein-restricted animals exhibited significantly smaller fetal body weight and brain cortical thickness than controls. At birth and thereafter, body weight was
Changes in Connectivity after Visual Cortical Brain Damage Underlie Altered Visual Function
ERIC Educational Resources Information Center
Bridge, Holly; Thomas, Owen; Jbabdi, Saad; Cowey, Alan
The full extent of the brain's ability to compensate for damage or changed experience is yet to be established. One question particularly important for evaluating and understanding rehabilitation following brain damage is whether recovery involves new and aberrant neural connections or whether any change in function is due to the functional…
The antidepressant tranylcypromine alters cellular proliferation and migration in the adult goldfish brain.
Romanczyk, Tara B; Jacobowitz, David M; Pollard, Harvey B; Wu, Xingjia; Anders, Juanita J
The goldfish (Carassius auratus) is a widely studied vertebrate model organism for studying cell proliferation in the adult brain, and provide the experimental advantage of growing their body and brain throughout their ?30-year life time. Cell proliferation occurs in the teleost brain in widespread proliferation zones. Increased cell proliferation in the brain has been linked to the actions of certain antidepressants, including tranylcypromine (TCP), which is used in the treatment of depression. We hypothesized that proliferation zones in the adult goldfish brain can be used to determine the antidepressant effects on cellular proliferation. Here, we report that bromodeoxyuridine (BrdU) labeling over a 24-hr period can be used to rapidly identify the proliferation zones throughout the goldfish brain, including the telencephalon, diencephalon, optic tectal lobes, cerebellum, and facial and vagal lobes. In the first 24 hr of BrdU administration, TCP caused an approximate and significant doubling of labeled cells in the combined brain regions examined, as detected by BrdU immunohistochemistry. TCP caused the greatest increase in cell proliferation in the cerebellum. The normal migratory paths of the proliferating cells within the cerebellum were not affected by TCP treatment. These results indicate that the goldfish provide significant advantages as a vertebrate model for rapidly investigating the effects of antidepressant drugs on cellular proliferation and migration in the normal and injured brain. PMID:24816924
Age and Haplotype Variations within FADS1 Interact and Associate with Alterations in Fatty Acid Composition in Human Male Cortical Brain Tissue
Erika Freemantle; Aleksandra Lalovic; Naguib Mechawar; Gustavo Turecki
Fatty acids (FA) play an integral role in brain function and alterations have been implicated in a variety of complex neurological disorders. Several recent genomic studies have highlighted genetic variability in the fatty acid desaturase (FADS1\\/2\\/3) gene cluster as an important contributor to FA alterations in serum lipids as well as measures of FA desaturase index estimated by ratios of
Clinical Significance of Basal Ganglia Alterations at Brain MRI and 1 H MRS in Cirrhosis and Role in the Pathogenesis of Hepatic Encephalopathy
Laurent Spahr; Pierre R. Burkhard; Hannelore Grötzsch; Antoine Hadengue
In hepatic encephalopathy, a progressive and diffuse impairment in brain function is associated with gradual alterations that can be detected by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H MRS). In some patients, a variety of movement disorders suggestive of extrapyramidal impairment points toward basal ganglia (BG) alterations. Accordingly, (i) hyperintensities at MRI predominant in the pallidum, an
Alterations of serum brain type natriuretic peptide (BNP) in patients with Crimean-Congo hemorrhagic fever
Uysal, Elif Bilge; Sancakdar, Enver; ?eker, Ay?e; Deveci, Köksal; Tuzcu, Nevin; Karap?nar, Hekim
Background: Crimean-Congo hemorrhagic fever (CCHF) is known to be associated with cardiac damage. Brain type natriuretic peptide (BNP) is secreted from stressed myocardium. Objectives: This study investigated that BNP levels in CCHF and its association with clinical course of disease. Methods: Consecutive CCHF diagnosis confirmed patients were enrolled to the study. Results of patients were compared with age-sex-matched healthy volunteers. Blood samples for BNP levels were collected from the patients during emergency room applications. Mortality, hospitalization duration and other disease severity predictors (thrombocyte count, hemoglobin, white blood cell count, alanine aminotransferase, aspartate aminotransferase, prothrombin time, lactate dehydrogenase, international normalized ratio, activated partial thromboplastin time) were recorded. These parameters' correlations with BNP levels were analyzed. Result: Forty-three CCHF patients and 28 control subjects recruited to the study. Groups were similar for age and gender. There was no mortality. Levels of BNP were found to be significantly higher in patients than control subjects (100.4±45.4 vs. 78.0±40.4, P=0.033). But BNP levels were not correlated with duration of hospitalization and disease severity predictors (P > 0.05). Conclusions: This study showed that BNP levels are modestly increased in CCHF but this increase does not correlated with disease severity predictors. PMID:25932235
Alterations in alpha-adrenergic and muscarinic cholinergic receptor binding in rat brain following nonionizing radiation
Gandhi, V.C.; Ross, D.H.
Microwave radiation produces hyperthermia. The mammalian thermoregulatory system defends against changes in temperature by mobilizing diverse control mechanisms. Neurotransmitters play a major role in eliciting thermoregulatory responses. The involvement of adrenergic and muscarinic cholinergic receptors was investigated in radiation-induced hyperthermia. Rats were subjected to radiation at 700 MHz frequency and 15 mW/cm/sup 2/ power density and the body temperature was raised by 2.5 degrees C. Of six brain regions investigated only the hypothalamus showed significant changes in receptor states, confirming its pivotal role in thermoregulation. Adrenergic receptors, studied by (/sup 3/H)clonidine binding, showed a 36% decrease in binding following radiation after a 2.5 degrees C increase in body temperature, suggesting a mechanism to facilitate norepinephrine release. Norepinephrine may be speculated to maintain thermal homeostasis by activating heat dissipation. Muscarinic cholinergic receptors, studied by (3H)quinuclidinyl benzilate binding, showed a 65% increase in binding at the onset of radiation. This may be attributed to the release of acetylcholine in the hypothalamus in response to heat cumulation. The continued elevated binding during the period of cooling after radiation was shut off may suggest the existence of an extra-hypothalamic heat-loss pathway.
Chronic neck pain alters muscle activation patterns to sudden movements.
Boudreau, Shellie A; Falla, Deborah
The aim of this study was to assess the activation of the sternocleidomastoid (SCM) and splenius capitis (SC) muscles in response to unanticipated, full body perturbations in individuals with chronic neck pain (NP) and age-matched healthy controls (HC). Individuals with NP had a history of NP for 8.9 ± 7.8 years, rated the intensity of NP as 4.2 ± 2.0 (score out of 10), and scored 15.3 ± 6.5 on the Neck Disability Index. Participants stood on a moveable platform during which 32 randomized postural perturbations (eight repetitions of four perturbation types: 8 cm forward slide (FS), 8 cm backward slides, 10° forward tilt, and 10° backward tilt) with varying inter-perturbation time intervals were performed over a period of 5 min. Bilateral surface electromyography (EMG) from the SCM and SC was recorded, and the onset time and the average rectified value of the EMG signal was determined for epochs of 100 ms; starting 100 ms prior to and 500 ms after the perturbation onset. Individuals with NP, as compared to HC, demonstrated delayed onset times and reduced EMG amplitude of the SCM and SC muscles in response to all postural perturbations. Such findings were most pronounced following the FS postural perturbation (healthy vs. NP for SCM 83.3 ± 8.0 vs. 86.3 ± 4.4 and SC 75.6 ± 3.5 vs. 89.3 ± 4.2), which was also associated with the greatest change (expressed in % relative to baseline) in EMG amplitude (healthy vs. NP for SCM 206.6 ± 50.4 vs. 115.9 ± 15.7 and SC 83.4 ± 19.2 vs. 69.2 ± 10.9) across all postural perturbations types. Individuals with NP display altered neural control of the neck musculature in response to rapid, unanticipated full body postural perturbations. Although the relative timing of neck musculature activity in individuals with NP appears to be intact, simultaneous co-activation of the neck musculature emerges for unanticipated anterior-posterior postural perturbations. PMID:24632836
Concomitant treatment of brain metastasis with Whole Brain Radiotherapy [WBRT] and Temozolomide [TMZ] is active and improves Quality of Life
Raffaele Addeo; Michele Caraglia; Vincenzo Faiola; Elena Capasso; Bruno Vincenzi; Liliana Montella; Rosario Guarrasi; Luigi Caserta; Salvatore Del Prete
BACKGROUND: Brain metastases (BM) represent one of the most frequent complications related to cancer, and their treatment continues to evolve. We have evaluated the activity, toxicity and the impact on Quality of Life (QoL) of a concomitant treatment with whole brain radiotherapy (WBRT) and Temozolomide (TMZ) in patients with brain metastases from solid tumors in a prospective Simon two stage
Methamphetamine Causes Microglial Activation in the Brains of Human Abusers
Sekine, Yoshimoto; Ouchi, Yasuomi; Sugihara, Genichi; Takei, Nori; Yoshikawa, Etsuji; Nakamura, Kazuhiko; Iwata, Yasuhide; Tsuchiya, Kenji J.; Suda, Shiro; Suzuki, Katsuaki; Kawai, Masayoshi; Takebayashi, Kiyokazu; Yamamoto, Shigeyuki; Matsuzaki, Hideo; Ueki, Takatoshi; Mori, Norio; Gold, Mark S.; Cadet, Jean L.
Methamphetamine is a popular addictive drug whose use is associated with multiple neuropsychiatric adverse events and toxic to the dopaminergic and serotonergic systems of the brain. Methamphetamine-induced neuropathology is associated with increased expression of microglial cells that are thought to participate in either pro-toxic or protective mechanisms in the brain. Although reactive microgliosis has been observed in animal models of methamphetamine neurotoxicity, no study has reported on the status of microglial activation in human methamphetamine abusers. The present study reports on 12 abstinent methamphetamine abusers and 12 age-, gender-, education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [11C](R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) ([11C](R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials of [11C](R)-PK11195 in brain regions with dopaminergic and/or serotonergic innervation. The mean levels of [11C](R)-PK11195 binding were higher in methamphetamine abusers than those in control subjects in all brain regions (> 250% higher, p < 0.01 for all). In addition, the binding levels in the midbrain, striatum, thalamus, and orbitofrontal and insular cortices (p < 0.05) correlated inversely with the duration of methamphetamine abstinence. These results suggest that chronic self-administration of methamphetamine can cause reactive microgliosis in the brains of human methamphetamine abusers, a level of activation that appears to subside over longer periods of abstinence. PMID:18509037
Hippocampal Inactivation with TTX Impairs Long-Term Spatial Memory Retrieval and Modifies Brain Metabolic Activity
Conejo, Nélida María; Cimadevilla, José Manuel; González-Pardo, Héctor; Méndez-Couz, Marta; Arias, Jorge Luis
Functional inactivation techniques enable studying the hippocampal involvement in each phase of spatial memory formation in the rat. In this study, we applied tetrodotoxin unilaterally or bilaterally into the dorsal hippocampus to evaluate the role of this brain structure in retrieval of memories acquired 28 days before in the Morris water maze. We combined hippocampal inactivation with the assessment of brain metabolism using cytochrome oxidase histochemistry. Several brain regions were considered, including the hippocampus and other related structures. Results showed that both unilateral and bilateral hippocampal inactivation impaired spatial memory retrieval. Hence, whereas subjects with bilateral hippocampal inactivation showed a circular swim pattern at the side walls of the pool, unilateral inactivation favoured swimming in the quadrants adjacent to the target one. Analysis of cytochrome oxidase activity disclosed regional differences according to the degree of hippocampal functional blockade. In comparison to control group, animals with bilateral inactivation showed increased CO activity in CA1 and CA3 areas of the hippocampus during retrieval, while the activity of the dentate gyrus substantially decreased. However, unilateral inactivated animals showed decreased CO activity in Ammon's horn and the dentate gyrus. This study demonstrated that retrieval recruits differentially the hippocampal subregions and the balance between them is altered with hippocampal functional lesions. PMID:23724089
Brain, Liver, and Serum Salusin-alpha and -beta Alterations in Sprague-Dawley Rats with or without Metabolic Syndrome
Citil, Cihan; Konar, Vahit; Aydin, Suleyman; Yilmaz, Musa; Albayrak, Serdal; Ozercan, Ibrahim Hanifi; Ozkan, Yusuf
Background This metabolic syndrome (MetS) study was designed to investigate changes in expression of the neuropeptides salusin-? (Sal-?) and salusin-? (Sal-?) in brain and liver tissue in response to obesity and related changes induced by high-fructose diet and explored how these changes were reflected in the circulating levels of Sal-? and Sal-?, as well as revealing how the lipid profile and concentrations of glucose and uric acid were altered. Material/Methods The study included 14 Sprague-Dawley rats. The control group was fed ad libitum on standard rat pellets, while the intervention group was given water with 10% fructose in addition to the standard rat pellet for 3 months. Sal-? and Sal-? concentrations in the serum and tissue supernatants were measured by ELISA, and immunohistochemical staining was used to demonstrate expression of the hormones in brain and liver. Results Sal-? and Sal-? levels in both the serum and the brain and liver tissue supernatants were lower in the MetS group than the control group. Sal-? and Sal-? were shown by immunohistochemistry to be produced in the brain epithelium, the supraoptic nucleus of the hypothalamus, and the liver hepatocytes. Conclusions The decrease in Sal-? and Sal-? might be involved in the etiopathology of the metabolic syndrome induced by fructose. PMID:25070707
Stress during pregnancy alters dendritic spine density and gene expression in the brain of new-born lambs.
Petit, Bérengčre; Boissy, Alain; Zanella, Adroaldo; Chaillou, Elodie; Andanson, Stéphane; Bes, Sébastien; Lévy, Frédéric; Coulon, Marjorie
Rodent studies show how prenatal stress (PS) can alter morphology in the cortico-limbic structures that support emotional and cognitive functions. PS-induced alteration is less well described in species with a gyrencephalic brain and complex earlier fetal development, and never in sheep at birth to rule out postnatal environment effects or influences of maternal behavior. This study aimed to assess the consequences of a mild chronic stress in pregnant ewes on the neurobiological development of their lambs at birth. During the last third of gestation, 7 ewes were exposed daily to various unpredictable and negative routine management-based challenges (stressed group), while 7 other ewes were housed without any additional perturbation (control group). For each group, a newborn from each litter was sacrificed at birth to collect its brain and analyze its expression levels of genes involved in neuronal dendritic morphology (Dlg4, Rac1, RhoA, Doc2b), synaptic transmission (Nr1, Grin2A, Grin2B) and glucocorticoid receptor (Nr3C1) in hippocampus (HPC), prefrontal cortex (PFC) and amygdala (AMYG). Results revealed that lambs from stressed dam (PS lambs) showed under-expression of Rac1 and Nr1 in PFC and overexpression of Dlg4 in AMYG compared to controls. To assess the morphological consequences of gene dysregulations, the dendritic morphology of pyramidal neurons was explored by Golgi-Cox staining in HPC and PFC. PS lambs had higher dendritic spine density in both structures and more stubby-type spines in the CA1 area of HPC than controls. This is the first demonstration in sheep that PS alters fetal brain, possibly reflecting functional changes in synaptic transmission to cope with adversity experienced in fetal life. PMID:26005125
Identification of hematomas in mild traumatic brain injury using an index of quantitative brain electrical activity.
Prichep, Leslie S; Naunheim, Rosanne; Bazarian, Jeffrey; Mould, W Andrew; Hanley, Daniel
Rapid identification of traumatic intracranial hematomas following closed head injury represents a significant health care need because of the potentially life-threatening risk they present. This study demonstrates the clinical utility of an index of brain electrical activity used to identify intracranial hematomas in traumatic brain injury (TBI) presenting to the emergency department (ED). Brain electrical activity was recorded from a limited montage located on the forehead of 394 closed head injured patients who were referred for CT scans as part of their standard ED assessment. A total of 116 of these patients were found to be CT positive (CT+), of which 46 patients with traumatic intracranial hematomas (CT+) were identified for study. A total of 278 patients were found to be CT negative (CT-) and were used as controls. CT scans were subjected to quantitative measurements of volume of blood and distance of bleed from recording electrodes by blinded independent experts, implementing a validated method for hematoma measurement. Using an algorithm based on brain electrical activity developed on a large independent cohort of TBI patients and controls (TBI-Index), patients were classified as either positive or negative for structural brain injury. Sensitivity to hematomas was found to be 95.7% (95% CI = 85.2, 99.5), specificity was 43.9% (95% CI = 38.0, 49.9). There was no significant relationship between the TBI-Index and distance of the bleed from recording sites (F = 0.044, p = 0.833), or volume of blood measured F = 0.179, p = 0.674). Results of this study are a validation and extension of previously published retrospective findings in an independent population, and provide evidence that a TBI-Index for structural brain injury is a highly sensitive measure for the detection of potentially life-threatening traumatic intracranial hematomas, and could contribute to the rapid, quantitative evaluation and treatment of such patients. PMID:25054838
The social brain in adolescence
Sarah-Jayne Blakemore
The term 'social brain' refers to the network of brain regions that are involved in understanding others. Behaviour that is related to social cognition changes dramatically during human adolescence. This is paralleled by functional changes that occur in the social brain during this time, in particular in the medial prefrontal cortex and the superior temporal sulcus, which show altered activity
[Alterations in brain distribution of methamphetamine in methamphetamine-sensitized animals].
Mizugaki, M
[11C]Methamphetamine ([11C]MAP) was synthesized by an automated on-line [11C]methylation system for a position emission tomography (PET) study. The author newly prepared a MAP-sensitized dog by repeated treatment of MAP, and studied the brain distribution of [11C]MAP in normal and MAP.sensitized dogs. The maximal level of accumulation of [11C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. No difference was found in the metabolism of MAP between the two conditions. A significant increase in [11C]MAP uptake into the sensitized dog brain was prevented by haloperidol and cocaine pretreatments. These results suggest that changes in the pharmacokinetic profile of MAP in the brain affect the development or expression of MAP-induced behavioral sensitization. PMID:8962438
Active tactile exploration enabled by a brain-machine-brain interface
O'Doherty, Joseph E.; Lebedev, Mikhail A.; Ifft, Peter J.; Zhuang, Katie Z.; Shokur, Solaiman; Bleuler, Hannes; Nicolelis, Miguel A. L.
Brain-machine interfaces (BMIs)1,2 use neuronal activity recorded from the brain to establish direct communication with external actuators, such as prosthetic arms. While BMIs aim to restore the normal sensorimotor functions of the limbs, so far they have lacked tactile sensation. Here we demonstrate the operation of a brain-machine-brain interface (BMBI) that both controls the exploratory reaching movements of an actuator and enables the signalling of artificial tactile feedback through intracortical microstimulation (ICMS) of the primary somatosensory cortex (S1). Monkeys performed an active-exploration task in which an actuator (a computer cursor or a virtual-reality hand) was moved using a BMBI that derived motor commands from neuronal ensemble activity recorded in primary motor cortex (M1). ICMS feedback occurred whenever the actuator touched virtual objects. Temporal patterns of ICMS encoded the artificial tactile properties of each object. Neuronal recordings and ICMS epochs were temporally multiplexed to avoid interference. Two monkeys operated this BMBI to search and discriminate one out of three visually undistinguishable objects, using the virtual hand to identify the unique artificial texture (AT) associated with each. These results suggest that clinical motor neuroprostheses might benefit from the addition of ICMS feedback to generate artificial somatic perceptions associated with mechanical, robotic, or even virtual prostheses. PMID:21976021
Altered frontocingulate activation during aversive interoceptive processing in young adults transitioning to problem stimulant use
Stewart, Jennifer L.; Parnass, Jason M.; May, April C.; Davenport, Paul W.; Paulus, Martin P.
Problems associated with stimulant use have been linked to frontocingulate, insular, and thalamic dysfunction during decision making and alterations in interoceptive processing. However, little is known about how interoception and decision making interact and contribute to dysfunctions that promote the transition from recreational drug use to abuse or dependence. Here, we investigate brain activation in response to reward, punishment, and uncertainty during an aversive interoceptive challenge in current and former stimulant (cocaine and amphetamine) users using functional magnetic resonance imaging (fMRI). Young adults previously identified as recreational users (n = 184) were followed up 3 years later. Of these, 18 individuals progressed to problem stimulant use (PSU), whereas 15 desisted stimulant use (DSU). PSU, DSU, and 14 healthy comparison subjects (CTL) performed a two-choice prediction task at three fixed error rates (20% = reward, 50% = uncertainty, 80% = punishment) during which they anticipated and experienced episodes of inspiratory breathing load. Although groups did not differ in insula activation or subjective breathing load ratings, PSU exhibited lower right inferior frontal gyrus (IFG) and bilateral anterior cingulate (ACC) activation than DSU and CTL during aversive interoceptive processing as well as lower right IFG in response to decision making involving uncertainty. However, PSU exhibited greater bilateral IFG activation than DSU and CTL while making choices within the context of punishing feedback, and both PSU and DSU showed lower thalamic activation during breathing load than CTL. Findings suggest that frontocingulate attenuation, reflecting reduced resources devoted to goal maintenance and action selection in the presence of uncertainty and interoceptive perturbations, may be a biomarker for susceptibility to PSU. PMID:24298242
Brief Communications Brain Monoamine Oxidase A Activity Predicts Trait
Goldstein, Rita
aggression. Brain MAO A activity was measured in vivo in healthy non- smoking men with positron emission-third of the variability. Because trait aggression is a measure used to predict antisocial behavior, these results under), it may also provide an explanation for the high rate of cigarette smoking in depression (Glassman et al
Brain Activation during Sentence Comprehension among Good and Poor Readers
Ann Meyler; Timothy A. Keller; Vladimir L. Cherkassky; Donghoon Lee; Fumiko Hoeft; Susan Whitfield-Gabrieli; John D. E. Gabrieli; Marcel Adam Just
This study sought to increase current understanding of the neuro- psychological basis of poor reading ability by using fMRI to examine brain activation during a visual sentence comprehension task among good and poor readers in the third (n 5 32) and fifth (n 5 35) grades. Reading ability, age, and the combination of both factors made unique contributions to cortical
Brain Activity while Reading Sentences with Kanji Characters Expressing Emotions
Masahide Yuasa; Keiichi Saito; Naoki Mukawa
In this paper, we describe the brain activity associated with kanji characters expressing emotion, which are places at the end of a sentence. Japanese people use a special kanji character in brackets at the end of sentences in text messages such as those sent through e-mail and messenger tools. Such kanji characters plays a role to expresses the sender's emotion
Learning to See Biological Motion: Brain Activity Parallels Behavior
Emily D. Grossman; Randolph Blake; Chai-Youn Kim
Individuals improve with practice on a variety of perceptual tasks, presumably reflecting plasticity in underlying neural mechanisms. We trained observers to discriminate biological motion from scrambled (nonbiological) motion and examined whether the resulting improvement in perceptual performance was accompanied by changes in activation within the posterior superior temporal sulcus and the fusiform face area, brain areas involved in perception of
On a Mathematical Model of Brain Activities
Fichtner, K.-H. [Friedrich Schiller Unversity Jena, Institute of Applied Mathematics, E.-Abbe-Platz 2, 07743 Jena (Germany); Fichtner, L. [Friedrich Schiller Unversity Jena, Institute of Psychology, Am Steiger 3, 07743 Jena (Germany); Freudenberg, W. [Brandenb. Techn. University Cottbus, Dep. of Mathematics, PO box 10 13 44, 03013 Cottbus (Germany); Ohya, M. [Tokyo University of Science, Department of Information Science, Noda City, Chiba 278-8510 (Japan)
The procedure of recognition can be described as follows: There is a set of complex signals stored in the memory. Choosing one of these signals may be interpreted as generating a hypothesis concerning an 'expexted view of the world'. Then the brain compares a signal arising from our senses with the signal chosen from the memory leading to a change of the state of both signals. Furthermore, measurements of that procedure like EEG or MEG are based on the fact that recognition of signals causes a certain loss of excited neurons, i.e. the neurons change their state from 'excited' to 'nonexcited'. For that reason a statistical model of the recognition process should reflect both--the change of the signals and the loss of excited neurons. A first attempt to explain the process of recognition in terms of quantum statistics was given. In the present note it is not possible to present this approach in detail. In lieu we will sketch roughly a few of the basic ideas and structures of the proposed model of the recognition process (Section). Further, we introduce the basic spaces and justify the choice of spaces used in this approach. A more elaborate presentation including all proofs will be given in a series of some forthcoming papers. In this series also the procedures of creation of signals from the memory, amplification, accumulation and transformation of input signals, and measurements like EEG and MEG will be treated in detail.
Chemotherapy Altered Brain Functional Connectivity in Women with Breast Cancer: A Pilot Study
Dumas, Julie A.; Makarewicz, Jenna; Schaubhut, Geoffrey J.; Devins, Robert; Albert, Kimberly; Dittus, Kim; Newhouse, Paul A.
Adjuvant chemotherapy is associated with improvements in long-term cancer survival. However, reports of cognitive impairment following treatment emphasize the importance of understanding the long-term effects of chemotherapy on brain functioning. Cognitive deficits found in chemotherapy patients suggest a change in brain functioning that affects specific cognitive domains such as attentional processing and executive functioning. This study examined the processes potentially underlying these changes in cognition by examining brain functional connectivity pre- and post-chemotherapy in women with breast cancer. Functional connectivity examines the temporal correlation between spatially remote brain regions in an effort to understand how brain networks support specific cognitive functions. Nine women diagnosed with breast cancer completed a functional magnetic resonance imaging (fMRI) session before chemotherapy, one month after, and one year after the completion of chemotherapy. Seed-based functional connectivity analyses were completed using seeds in the intraparietal sulcus (IPS) to examine connectivity in the dorsal anterior attention network and in the posterior cingulate cortex (PCC) to examine connectivity in the default mode network. Results showed decreased functional connectivity one month after chemotherapy that partially returned to baseline at one year in the dorsal attention network. Decreased connectivity was seen in the default mode network at one month and one year following chemotherapy. In addition, increased subjective memory complaints were noted at one month and one year post-chemotherapy. These findings suggest a detrimental effect of chemotherapy on brain functional connectivity that is potentially related to subjective cognitive assessment. PMID:23852814
Use of brain electrical activity for the identification of hematomas in mild traumatic brain injury.
Hanley, Daniel F; Chabot, Robert; Mould, W Andrew; Morgan, Timothy; Naunheim, Rosanne; Sheth, Kevin N; Chiang, William; Prichep, Leslie S
This study investigates the potential clinical utility in the emergency department (ED) of an index of brain electrical activity to identify intracranial hematomas. The relationship between this index and depth, size, and type of hematoma was explored. Ten minutes of brain electrical activity was recorded from a limited montage in 38 adult patients with traumatic hematomas (CT scan positive) and 38 mild head injured controls (CT scan negative) in the ED. The volume of blood and distance from recording electrodes were measured by blinded independent experts. Brain electrical activity data were submitted to a classification algorithm independently developed traumatic brain injury (TBI) index to identify the probability of a CT+traumatic event. There was no significant relationship between the TBI-Index and type of hematoma, or distance of the bleed from recording sites. A significant correlation was found between TBI-Index and blood volume. The sensitivity to hematomas was 100%, positive predictive value was 74.5%, and positive likelihood ratio was 2.92. The TBI-Index, derived from brain electrical activity, demonstrates high accuracy for identification of traumatic hematomas. Further, this was not influenced by distance of the bleed from the recording electrodes, blood volume, or type of hematoma. Distance and volume limitations noted with other methods, (such as that based on near-infrared spectroscopy) were not found, thus suggesting the TBI-Index to be a potentially important adjunct to acute assessment of head injury. Because of the life-threatening risk of undetected hematomas (false negatives), specificity was permitted to be lower, 66%, in exchange for extremely high sensitivity. PMID:24040943
Blue Light Stimulates Cognitive Brain Activity in Visually Blind Individuals
Vandewalle, Gilles; Collignon, Olivier; Hull, Joseph T.; Daneault, Véronique; Albouy, Genevičve; Lepore, Franco; Phillips, Christophe; Doyon, Julien; Czeisler, Charles A.; Dumont, Marie; Lockley, Steven W.; Carrier, Julie
Light regulates multiple non-image-forming (or non-visual) circadian, neuroendocrine and neurobehavioral functions, via outputs from intrinsically-photosensitive retinal ganglion cells (ipRGCs). Exposure to light directly enhances alertness and performance, so that light is an important regulator of wakefulness and cognition. The roles of rods, cones and ipRGCs in the impact of light on cognitive brain functions remain unclear, however. A small percentage of blind individuals retain non-image-forming photoreception and offer a unique opportunity to investigate light impacts in the absence of conscious vision, presumably through ipRGCs. Here, we show that three such patients were able to choose non-randomly about the presence of light despite their complete lack of sight. Furthermore, 2s of blue light modified EEG activity when administered simultaneously to auditory stimulations. FMRI further showed that, during an auditory working memory task, less than a minute of blue light triggered the recruitment of supplemental prefrontal and thalamic brain regions involved in alertness and cognition regulation, as well as key areas of the default mode network. These results, which have to be considered as a proof of concept, show that non-image-forming photoreception triggers some awareness for light and can have a more rapid impact on human cognition than previously understood, if brain processing is actively engaged. Furthermore, light stimulates higher cognitive brain activity, independently of vision, and engages supplemental brain areas to perform an ongoing cognitive process. To our knowledge, our results constitute the first indication that ipRGC signaling may rapidly affect fundamental cerebral organization, so that it could potentially participate to the regulation of numerous aspects of human brain function. PMID:23859643
An update of the classical and novel methods used for measuring fast neurotransmitters during normal and brain altered function.
Cifuentes Castro, Victor Hugo; López Valenzuela, Carmen Lucía; Salazar Sánchez, Juan Carlos; Peńa, Kenia Pardo; López Pérez, Silvia J; Ibarra, Jorge Ortega; Villagrán, Alberto Morales
To understand better the cerebral functions, several methods have been developed to study the brain activity, they could be related with morphological, electrophysiological, molecular and neurochemical techniques. Monitoring neurotransmitter concentration is a key role to know better how the brain works during normal or pathological conditions, as well as for studying the changes in neurotransmitter concentration with the use of several drugs that could affect or reestablish the normal brain activity. Immediate response of the brain to environmental conditions is related with the release of the fast acting neurotransmission by glutamate (Glu), ?-aminobutyric acid (GABA) and acetylcholine (ACh) through the opening of ligand-operated ion channels. Neurotransmitter release is mainly determined by the classical microdialysis technique, this is generally coupled to high performance liquid chromatography (HPLC). Detection of neurotransmitters can be done by fluorescence, optical density, electrochemistry or other detection systems more sophisticated. Although the microdialysis method is the golden technique to monitor the brain neurotransmitters, it has a poor temporal resolution. Recently, with the use of biosensor the drawback of temporal resolution has been improved considerably, however other inconveniences have merged, such as stability, reproducibility and the lack of reliable biosensors mainly for GABA. The aim of this review is to show the important advances in the different ways to measure neurotransmitter concentrations; both with the use of classic techniques as well as with the novel methods and alternant approaches to improve the temporal resolution. PMID:25977677
An Update of the Classical and Novel Methods Used for Measuring Fast Neurotransmitters During Normal and Brain Altered Function
Cifuentes Castro, Victor Hugo; López Valenzuela, Carmen Lucía; Salazar Sánchez, Juan Carlos; Peńa, Kenia Pardo; López Pérez, Silvia J.; Ibarra, Jorge Ortega; Villagrán, Alberto Morales
To understand better the cerebral functions, several methods have been developed to study the brain activity, they could be related with morphological, electrophysiological, molecular and neurochemical techniques. Monitoring neurotransmitter concentration is a key role to know better how the brain works during normal or pathological conditions, as well as for studying the changes in neurotransmitter concentration with the use of several drugs that could affect or reestablish the normal brain activity. Immediate response of the brain to environmental conditions is related with the release of the fast acting neurotransmission by glutamate (Glu), ?-aminobutyric acid (GABA) and acetylcholine (ACh) through the opening of ligand-operated ion channels. Neurotransmitter release is mainly determined by the classical microdialysis technique, this is generally coupled to high performance liquid chromatography (HPLC). Detection of neurotransmitters can be done by fluorescence, optical density, electrochemistry or other detection systems more sophisticated. Although the microdialysis method is the golden technique to monitor the brain neurotransmitters, it has a poor temporal resolution. Recently, with the use of biosensor the drawback of temporal resolution has been improved considerably, however other inconveniences have merged, such as stability, reproducibility and the lack of reliable biosensors mainly for GABA. The aim of this review is to show the important advances in the different ways to measure neurotransmitter concentrations; both with the use of classic techniques as well as with the novel methods and alternant approaches to improve the temporal resolution. PMID:25977677
Brain activation during micturition in women
Bertil F. M. Blok; Leontien M. Sturms; Gert Holstege
Summary Experiments in the cat have led to a concept of how the CNS controls micturition. In a previous study this concept was tested in a PET study in male volunteers. It was demonstrated that specific brainstem and forebrain areas are activated during micturition. It was unfortunate that this study did not involve women, because such results are important for
Platelets Alter Gene Expression Profile in Human Brain Endothelial Cells in an In Vitro Model of Cerebral Malaria
Barbier, Mathieu; Faille, Dorothée; Loriod, Béatrice; Textoris, Julien; Camus, Claire; Puthier, Denis; Flori, Laurence; Wassmer, Samuel Crocodile; Victorero, Genevičve; Alessi, Marie-Christine; Fusaď, Thierry; Nguyen, Catherine; Grau, Georges E.; Rihet, Pascal
Platelet adhesion to the brain microvasculature has been associated with cerebral malaria (CM) in humans, suggesting that platelets play a role in the pathogenesis of this syndrome. In vitro co-cultures have shown that platelets can act as a bridge between Plasmodium falciparum-infected red blood cells (pRBC) and human brain microvascular endothelial cells (HBEC) and potentiate HBEC apoptosis. Using cDNA microarray technology, we analyzed transcriptional changes of HBEC in response to platelets in the presence or the absence of tumor necrosis factor (TNF) and pRBC, which have been reported to alter gene expression in endothelial cells. Using a rigorous statistical approach with multiple test corrections, we showed a significant effect of platelets on gene expression in HBEC. We also detected a strong effect of TNF, whereas there was no transcriptional change induced specifically by pRBC. Nevertheless, a global ANOVA and a two-way ANOVA suggested that pRBC acted in interaction with platelets and TNF to alter gene expression in HBEC. The expression of selected genes was validated by RT-qPCR. The analysis of gene functional annotation indicated that platelets induce the expression of genes involved in inflammation and apoptosis, such as genes involved in chemokine-, TREM1-, cytokine-, IL10-, TGF?-, death-receptor-, and apoptosis-signaling. Overall, our results support the hypothesis that platelets play a pathogenic role in CM. PMID:21603600
Regional Homogeneity of Intrinsic Brain Activity in Happy and Unhappy Individuals
Luo, Yangmei; Huang, Xiting; Yang, Zhen; Li, Baolin; Liu, Jie; Wei, Dongtao
Background Why are some people happier than others? This question has intrigued many researchers. However, limited work has addressed this question within a neuroscientific framework. Methods The present study investigated the neural correlates of trait happiness using the resting-state functional magnetic resonance imaging (rs-fMRI) approach. Specifically, regional homogeneity (ReHo) was examined on two groups of young adults: happy and unhappy individuals (N?=?25 per group). Results Decreased ReHo in unhappy relative to happy individuals was observed within prefrontal cortex, medial temporal lobe, superior temporal lobe, and retrosplenial cortex. In contrast, increased ReHo in unhappy relative to happy individuals was observed within the dorsolateral prefrontal cortex, middle cingulate gyrus, putamen, and thalamus. In addition, the ReHo within the left thalamus was negatively correlated with Chinese Happiness Inventory (CHI) score within the happy group. Limitations As an exploratory study, we examined how general trait happiness is reflected in the regional homogeneity of intrinsic brain activity in a relatively small sample. Examining other types of happiness in a larger sample using a multitude of intrinsic brain activity indices are warranted for future work. Conclusions The local synchronization of BOLD signal is altered in unhappy individuals. The regions implicated in this alteration partly overlapped with previously identified default mode network, emotional circuitry, and rewarding system, suggesting that these systems may be involved in happiness. PMID:24454814
Brain temperature fluctuation: a reflection of functional neural activation.
Kiyatkin, Eugene A; Brown, P Leon; Wise, Roy A
Although it is known that relatively large increases in local brain temperature can occur during behaviour and in response to various novel, stressful and emotionally arousing environmental stimuli, the source of this heat is not clearly established. To clarify this issue, we monitored the temperature in three brain structures (dorsal and ventral striatum, cerebellum) and in arterial blood at the level of the abdominal aorta in freely moving rats exposed to several environmental challenges ranging from traditional stressors to simple sensory stimuli (cage change, tail pinch, exposure to another male rat, a female rat, a mouse or an unexpected sound). We found that brain temperature was consistently higher than arterial blood temperature, and that brain temperature increased prior to, and to a greater extent than, the increase in blood temperature evoked by each test challenge. Thus, the local metabolic consequences of widely correlated neural activity appear to be the primary source of increases in brain temperature and a driving force behind the associated changes in body temperature. PMID:12153543
DOI: 10.1093/brain/awh199 Brain (2004), 127, 18111821 Cortical activation and synchronization during
temporal) area and reliably less activation than the control group in Broca's (left inferior frontal gyrus, more informally, Broca's area, was involved in a number of processes that could play an integratingDOI: 10.1093/brain/awh199 Brain (2004), 127, 18111821 Cortical activation and synchronization
Effects of ionizing radiation on the blood brain barrier permeability to pharmacologically active substances
Trnovec, T.; Kallay, Z.; Bezek, S. (Institute of Experimental Pharmacology, Bratislava (Yugoslavia))
Ionizing radiation can impair the integrity of the blood brain barrier (BBB). Data on early and late damage after brain irradiation are usually reported separately, yet a gradual transition between these two types has become evident. Signs appearing within 3 weeks after irradiation are considered to be early manifestations. The mechanism of radiation-effected integrity impairment of the BBB is discussed in relation to changes in morphological structures forming the BBB, the endothelium of intracerebral vessels, and in the surrounding astrocytes. Alterations in the function of the BBB are manifested in the endothelium by changes in the ultrastructural location of the activity of phosphatases and by the activation of pinocytotic vesicular transport, and in astrocyte cytoplasm by glycogen deposition. The changes in ultrastructure were critically surveyed with regard to increasing doses of radiation to the brain in the range of 5 Gy to 960 Gy. The qualitative as well as the semiquantitative and quantitative observations on the passage of substances across the damaged BBB were treated separately. Qualitative changes are based mainly on findings of extravasation of vital stains and of labelled proteins. The quantitative studies established differences in radiation-induced changes in the permeability of the BBB depending on the structure and physico-chemical properties of the barrier penetrating tracers. Indirect evaluation of radiation-induced BBB changes is based on studies of pharmacological effects of substances acting on the CNS. In conclusion, radiation impairs significantly the integrity of the BBB following single irradiation of the brain with a dose exceeding 10-15 Gy. The response of the BBB to ionizing radiation is dependent both on the dose to which the brain is exposed and on specific properties of the tracer. 68 references.
Estradiol levels modulate brain activity and negative responses to psychosocial stress across the menstrual cycle.
Albert, Kimberly; Pruessner, Jens; Newhouse, Paul
Although ovarian hormones are thought to have a potential role in the well-known sex difference in mood and anxiety disorders, the mechanisms through which ovarian hormone changes contribute to stress regulation are not well understood. One mechanism by which ovarian hormones might impact mood regulation is by mediating the effect of psychosocial stress, which often precedes depressive episodes and may have mood consequences that are particularly relevant in women. In the current study, brain activity and mood response to psychosocial stress was examined in healthy, normally cycling women at either the high or low estradiol phase of the menstrual cycle. Twenty eight women were exposed to the Montreal Imaging Stress Task (MIST), with brain activity determined through functional magnetic resonance imaging, and behavioral response assessed with subjective mood and stress measures. Brain activity responses to psychosocial stress differed between women in the low versus high estrogen phase of the menstrual cycle: women with high estradiol levels showed significantly less deactivation in limbic regions during psychosocial stress compared to women with low estradiol levels. Additionally, women with higher estradiol levels also had less subjective distress in response to the MIST than women with lower estradiol levels. The results of this study suggest that, in normally cycling premenopausal women, high estradiol levels attenuate the brain activation changes and negative mood response to psychosocial stress. Normal ovarian hormone fluctuations may alter the impact of psychosocially stressful events by presenting periods of increased vulnerability to psychosocial stress during low estradiol phases of the menstrual cycle. This menstrual cycle-related fluctuation in stress vulnerability may be relevant to the greater risk for affective disorder or post-traumatic stress disorder in women. PMID:26123902
Convergent Findings of Altered Functional and Structural Brain Connectivity in Individuals with High Functioning Autism: A Multimodal MRI Study
Samson, Andrea C.; Kirsch, Valerie; Blautzik, Janusch; Grothe, Michel; Erat, Okan; Hegenloh, Michael; Coates, Ute; Reiser, Maximilian F.; Hennig-Fast, Kristina; Meindl, Thomas
Brain tissue changes in autism spectrum disorders seem to be rather subtle and widespread than anatomically distinct. Therefore a multimodal, whole brain imaging technique appears to be an appropriate approach to investigate whether alterations in white and gray matter integrity relate to consistent changes in functional resting state connectivity in individuals with high functioning autism (HFA). We applied diffusion tensor imaging (DTI), voxel-based morphometry (VBM) and resting state functional connectivity magnetic resonance imaging (fcMRI) to assess differences in brain structure and function between 12 individuals with HFA (mean age 35.5, SD 11.4, 9 male) and 12 healthy controls (mean age 33.3, SD 9.0, 8 male). Psychological measures of empathy and emotionality were obtained and correlated with the most significant DTI, VBM and fcMRI findings. We found three regions of convergent structural and functional differences between HFA participants and controls. The right temporo-parietal junction area and the left frontal lobe showed decreased fractional anisotropy (FA) values along with decreased functional connectivity and a trend towards decreased gray matter volume. The bilateral superior temporal gyrus displayed significantly decreased functional connectivity that was accompanied by the strongest trend of gray matter volume decrease in the temporal lobe of HFA individuals. FA decrease in the right temporo-parietal region was correlated with psychological measurements of decreased emotionality. In conclusion, our results indicate common sites of structural and functional alterations in higher order association cortex areas and may therefore provide multimodal imaging support to the long-standing hypothesis of autism as a disorder of impaired higher-order multisensory integration. PMID:23825652
Reovirus-mediated induction of ADAR1 (p150) minimally alters RNA editing patterns in discrete brain regions
Hood, Jennifer L.; Morabito, Michael V.; Martinez, Charles R.; Gilbert, James A.; Ferrick, Elizabeth A.; Ayers, Gregory D.; Chappell, James D.; Dermody, Terence S.; Emeson, Ronald B.
Transcripts encoding ADAR1, a double-stranded, RNA-specific adenosine deaminase involved in the adenosine-to-inosine (A-to-I) editing of mammalian RNAs, can be alternatively spliced to produce an interferon-inducible protein isoform (p150) that is up-regulated in both cell culture and in vivo model systems in response to pathogen or interferon stimulation. In contrast to other tissues, p150 is expressed at extremely low levels in the brain and it is unclear what role, if any, this isoform may play in the innate immune response of the central nervous system (CNS) or whether the extent of editing for RNA substrates critical for CNS function is affected by its induction. To investigate the expression of ADAR1 isoforms in response to viral infection and subsequent alterations in A-to-I editing profiles for endogenous ADAR targets, we used a neuro-tropic strain of reovirus to infect neonatal mice and quantify A-to-I editing in discrete brain regions using a multiplexed, high-throughput sequencing strategy. While intracranial injection of reovirus resulted in a widespread increase in the expression of ADAR1 (p150) in multiple brain regions and peripheral organs, significant changes in site-specific A-to-I conversion were quite limited, suggesting that steady-state levels of p150 expression are not a primary determinant for modulating the extent of editing for numerous ADAR targets in vivo. PMID:24906008
Altered Nrf2 Signaling Mediates Hypoglycemia-Induced Blood–Brain Barrier Endothelial Dysfunction In Vitro
Sajja, Ravi K.; Green, Kayla N.; Cucullo, Luca
Hypoglycemia impairs blood-brain barrier (BBB) endothelial function; a major hallmark in the pathogenesis of various CNS disorders. Previously, we have demonstrated that prolonged hypoglycemic exposure down-regulated BBB endothelial NF-E2 related factor-2 (Nrf2) expression; a redox-sensitive transcriptional factor that regulates endothelial function. Here, we sought to determine the functional role of Nrf2 in preserving BBB integrity and molecular mechanisms underlying hypoglycemia-induced Nrf2 down-regulation in vitro using human cerebral microvascular endothelial cell line (hCMEC/D3). Cell monolayers were exposed to normal or hypoglycemic (5.5 or 2.2mM D-glucose) media for 3-24h. Pharmacological or gene manipulation (by silencing RNA) approaches were used to investigate specific molecular pathways implicated in hypoglycemia-induced Nrf2 degradation. BBB integrity was assessed by paracellular permeability to labeled dextrans of increasing molecular sizes (4-70kDa). Silencing Nrf2 expression in hCMEC/D3 cells abrogated the expression of claudin-5 and VE-cadherin, while ZO-1 was up-regulated. These effects were paralleled by a decrease in electrical resistance of hCMEC/D3 monolayers and potential increase in permeability to all labeled dextrans. Hypoglycemic exposure (3-24h) led to progressive and sustained down-regulation of Nrf2 (without affecting mRNA) and its target, NQO-1, with a concomitant increase in the cytosolic pool of E3 ubiquitin ligase, Siah2 (but not Keap1). Pretreatment with protease inhibitor MG132, or selective knock-down of Siah2 (but not Keap1) significantly attenuated hypoglycemia-induced Nrf2 destabilization. While hypoglycemic exposure triggered a significant increase in BBB permeability to dextrans, silencing Siah2 gene abrogated the effects of hypoglycemia and restored BBB integrity. In summary, our data indicate a potential role for Nrf2 signaling in regulating tight junction integrity and maintaining BBB function. Nrf2 suppression by increased Siah2-driven proteasomal degradation mediates hypoglycemia-evoked endothelial dysfunction and loss of BBB integrity. Overall, this study suggests that sustained activation of endothelial Nrf2 signaling could have therapeutic potential to prevent hypoglycemia-induced cerebrovascular dysfunction. PMID:25807533
Altered neuronal activity relationships between the pedunculopontine nucleus and motor cortex in a rodent model of Parkinson's disease
Aravamuthan, Bhooma R.; Bergstrom, Debra A.; French, Robin A.; Taylor, Joseph J.; Parr-Brownlie, Louise C.; Walters, Judith R.
The pedunculopontine nucleus (PPN) is a new deep brain stimulation (DBS) target for Parkinson's disease (PD), but little is known about PPN firing pattern alterations in PD. The anesthetized rat is a useful model for investigating the effects of dopamine loss on the transmission of oscillatory cortical activity through basal ganglia structures. After dopamine loss, synchronous oscillatory activity emerges in the subthalamic nucleus and substantia nigra pars reticulata in phase with cortical slow oscillations. To investigate the impact of dopamine cell lesion-induced changes in basal ganglia output on activity in the PPN, this study examines PPN spike timing with reference to motor cortex (MCx) local field potential (LFP) activity in urethane- and ketamine-anesthetized rats. Seven – ten days after unilateral 6-hydroxydopamine lesion of the medial forebrain bundle, spectral power in PPN spike trains and coherence between PPN spiking and PPN LFP activity increased in the ?1 Hz range in urethane-anesthetized rats. PPN spike timing also changed from firing predominantly in-phase with MCx slow oscillations in the intact urethane-anesthetized rat to firing predominantly antiphase to MCx oscillations in the hemi-parkinsonian rat. These changes were not observed in the ketamine-anesthetized preparation. These observations suggest that dopamine loss alters PPN spike timing by increasing inhibitory oscillatory input to the PPN from basal ganglia output nuclei, a phenomenon that may be relevant to motor dysfunction and PPN DBS efficacy in PD patients. PMID:18601924
Fast transient networks in spontaneous human brain activity
Baker, Adam P; Brookes, Matthew J; Rezek, Iead A; Smith, Stephen M; Behrens, Timothy; Probert Smith, Penny J; Woolrich, Mark
To provide an effective substrate for cognitive processes, functional brain networks should be able to reorganize and coordinate on a sub-second temporal scale. We used magnetoencephalography recordings of spontaneous activity to characterize whole-brain functional connectivity dynamics at high temporal resolution. Using a novel approach that identifies the points in time at which unique patterns of activity recur, we reveal transient (100–200 ms) brain states with spatial topographies similar to those of well-known resting state networks. By assessing temporal changes in the occurrence of these states, we demonstrate that within-network functional connectivity is underpinned by coordinated neuronal dynamics that fluctuate much more rapidly than has previously been shown. We further evaluate cross-network interactions, and show that anticorrelation between the default mode network and parietal regions of the dorsal attention network is consistent with an inability of the system to transition directly between two transient brain states. DOI: http://dx.doi.org/10.7554/eLife.01867.001 PMID:24668169
Emotions promote social interaction by synchronizing brain activity across individuals.
Nummenmaa, Lauri; Glerean, Enrico; Viinikainen, Mikko; Jääskeläinen, Iiro P; Hari, Riitta; Sams, Mikko
Sharing others' emotional states may facilitate understanding their intentions and actions. Here we show that networks of brain areas "tick together" in participants who are viewing similar emotional events in a movie. Participants' brain activity was measured with functional MRI while they watched movies depicting unpleasant, neutral, and pleasant emotions. After scanning, participants watched the movies again and continuously rated their experience of pleasantness-unpleasantness (i.e., valence) and of arousal-calmness. Pearson's correlation coefficient was used to derive multisubject voxelwise similarity measures [intersubject correlations (ISCs)] of functional MRI data. Valence and arousal time series were used to predict the moment-to-moment ISCs computed using a 17-s moving average. During movie viewing, participants' brain activity was synchronized in lower- and higher-order sensory areas and in corticolimbic emotion circuits. Negative valence was associated with increased ISC in the emotion-processing network (thalamus, ventral striatum, insula) and in the default-mode network (precuneus, temporoparietal junction, medial prefrontal cortex, posterior superior temporal sulcus). High arousal was associated with increased ISC in the somatosensory cortices and visual and dorsal attention networks comprising the visual cortex, bilateral intraparietal sulci, and frontal eye fields. Seed-voxel-based correlation analysis confirmed that these sets of regions constitute dissociable, functional networks. We propose that negative valence synchronizes individuals' brain areas supporting emotional sensations and understanding of another's actions, whereas high arousal directs individuals' attention to similar features of the environment. By enhancing the synchrony of brain activity across individuals, emotions may promote social interaction and facilitate interpersonal understanding. PMID:22623534
Contributions of glycogen to astrocytic energetics during brain activation.
Dienel, Gerald A; Cruz, Nancy F
Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 ?mol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K(+) level, oxidative stress management, and memory consolidation; it is a multi-functional compound. PMID:24515302
Hormonal contraceptives masculinize brain activation patterns in the absence of behavioral changes in two numerical tasks.
Pletzer, Belinda; Kronbichler, Martin; Nuerk, Hans-Christoph; Kerschbaum, Hubert
The aim of the present study was to identify, whether and how oral hormonal contraceptives (OCs) alter women's number processing. Behavioral performance and brain activation patterns (BOLD-response) of 14 OC-users were evaluated during two distinct numerical tasks (number comparison, number bisection) and compared to 16 men (high testosterone), and 16 naturally cycling women, once during their follicular (low hormone levels) and once during their luteal cycle phase (high progesterone). For both tasks, reliable sex differences and menstrual cycle dependent modulation have previously been described. If progestogenic effects of the synthetic progestins contained in OC play a predominant role, OC-users should be comparable to luteal women. If androgenic effects of the synthetic steroids exert the progestogenic actions, OC-users should be comparable to men. Likewise, if neither of the above are the case, the reduction of endogenous steroids by OCs should make OC-users comparable to follicular women. Our findings suggest that OC-users resemble follicular women in their behavioral performance, but show male-like brain activation patterns during both tasks. Analysis of brain-behavior relationships suggests that OC-users differ from naturally cycling women in the way they recruit their neural resources to deal with challenges of the tasks. We conclude that OCs, which are used by 100 million women worldwide, may have profound effects on cognition that have not been recognized so far. PMID:24231554
Brain Proteomics Supports the Role of Glutamate Metabolism and Suggests Other Metabolic Alterations in Protein LIsoaspartyl
Clarke, Steven
Biochemistry and Biophysics, Karolinska Institutet, Scheeles vag 2, SE-17 177 Stockholm, Sweden Department-isoaspartyl methyltransferase (PIMT) repairs the isoaspartyl residues (isoAsp) that originate from asparagine deamidation to isoAsp accumulation in all tissues measured, especially in the brain. These PIMT-knockout (PIMT
High-throughput gene expression profiling of opioid-induced alterations in discrete brain areas.
Korostynski, Michal; Piechota, Marcin; Golda, Slawomir; Przewlocki, Ryszard
Whole-genome screening methods are unique approach to search for novel genes and molecular pathways involved in drug action. High-throughput profiling allows the gene expression levels of tens of thousands of transcripts to be measured simultaneously. Here, we describe transcriptional profiling in a specific area of the brain using DNA microarrays and next-generation sequencing. PMID:25293316
Fetal growth restriction caused by MIMT1 deletion alters brain transcriptome in cattle.
Venhoranta, Heli; Bauersachs, Stefan; Taponen, Juhani; Lohi, Hannes; Taira, Tomi; Andersson, Magnus; Kind, Alexander; Schnieke, Angelika; Flisikowski, Krzysztof
We examined levels of gene expression in the brains of bovine fetuses carrying a truncated MIMT1 allele, MIMT1(Del), shown to cause late abortion and stillbirth as a result of fetal growth restriction. MIMT1 is a non-protein coding gene that forms part of the imprinted PEG3 (paternally expressed gene 3) domain. Microarray analysis of brain cortex samples from mid-gestation MIMT1(Del/WT) bovine fetuses and wild-type siblings was performed to study the effect of fetal growth restriction on brain gene expression. Statistical analysis revealed 134 genes with increased mRNA levels and 22 with reduced levels in MIMT1(Del/WT) fetuses. Gene set enrichment analysis identified a relatively small number of significant functional clusters representing three major biological processes: response to oxidative stress, angiogenesis, and epithelial cell proliferation. Gene expression microarray analyses identified increased expression of VIPR2, HTRA1, S100A4 and MYH8 in fetuses carrying the deletion and decreased expression of DRD2, ADAM18, miR345, ZNF585A. ADAM18, DRD2 and S100A4 are known to be involved in prenatal brain development. ZNF585A, miR-345, VIPR2, HTRA1, and MYH8 are known to be involved in cell growth and differentiation, but any role in neural developmental has yet to be elucidated. PMID:23726833
Altered brain protein expression profiles are associated with molecular neurological dysfunction in the PKU mouse model
Imperlini, Esther; Orrů, Stefania; Corbo, Claudia; Daniele, Aurora; Salvatore, Francesco
Phenylketonuria (PKU), if not detected and treated in newborns, causes severe neurological dysfunction and cognitive and behavioral deficiencies. Despite the biochemical characterization of PKU, the molecular mechanisms underlying PKU-associated brain dysfunction remain poorly understood. The aim of this study was to gain insights into the pathogenesis of this neurological damage by analyzing protein expression profiles in brain tissue of Black and Tan BRachyury-PahEnu2 mice (a mouse model of PKU). We compared the cerebral protein expression of homozygous PKU mice with that of their heterozygous counterparts using two-dimensional difference gel electrophoresis analysis, and identified 21 differentially expressed proteins, four of which were over-expressed and 17 under-expressed. An in silico bioinformatic approach indicated that protein under-expression was related to neuronal differentiation and dendritic growth, and to such neurological disorders as progressive motor neuropathy and movement disorders. Moreover, functional annotation analyses showed that some identified proteins were involved in oxidative metabolism. To further investigate the proteins involved in the neurological damage, we validated two of the proteins that were most strikingly under-expressed, namely, Syn2 and Dpysl2, which are involved in synaptic function and neurotransmission. We found that Glu2/3 and NR1 receptor subunits were over-expressed in PKU mouse brain. Our results indicate that differential expression of these proteins may be associated with the processes underlying PKU brain dysfunction, namely, decreased synaptic plasticity and impaired neurotransmission. PMID:24548049
Chronic ethanol consumption profoundly alters regional brain ceramide and sphingomyelin content in rodents.
Roux, Aurelie; Muller, Ludovic; Jackson, Shelley N; Baldwin, Katherine; Womack, Virginia; Pagiazitis, John G; O'Rourke, Joseph R; Thanos, Panayotis K; Balaban, Carey; Schultz, J Albert; Volkow, Nora D; Woods, Amina S
Ceramides (CER) are involved in alcohol-induced neuroinflammation. In a mouse model of chronic alcohol exposure, 16 CER and 18 sphingomyelin (SM) concentrations from whole brain lipid extracts were measured using electrospray mass spectrometry. All 18 CER concentrations in alcohol exposed adults increased significantly (range: 25-607%); in juveniles, 6 CER decreased (range: -9 to -37%). In contrast, only three SM decreased in adult and one increased significantly in juvenile. Next, regional identification at 50 ?m spatial resolution from coronal sections was obtained with matrix implanted laser desorption/ionization mass spectrometry imaging (MILDI-MSI) by implanting silver nanoparticulate matrices followed by focused laser desorption. Most of the CER and SM quantified in whole brain extracts were detected in MILDI images. Coronal sections from three brain levels show qualitative regional changes in CER-SM ion intensities, as a function of group and brain region, in cortex, striatum, accumbens, habenula, and hippocampus. Highly correlated changes in certain white matter CER-SM pairs occur in regions across all groups, including the hippocampus and the lateral (but not medial) cerebellar cortex of adult mice. Our data provide the first microscale MS evidence of regional lipid intensity variations induced by alcohol. PMID:25387107
Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue
Ryten, Mina; Mamais, Adamantios; Trabzuni, Daniah; Manzoni, Claudia; McGoldrick, Philip; Chan, Diane; Dillman, Allissa; Zerle, Julia; Horan, Susannah; Taanman, Jan-Willem; Hardy, John; Marti-Masso, Jose-Felix; Healey, Daniel; Schapira, Anthony H.; Wolozin, Benjamin; Bandopadhyay, Rina; Cookson, Mark R.; van der Brug, Marcel P.; Lewis, Patrick A.
Point mutations in LRRK2 cause autosomal dominant Parkinson's disease. Despite extensive efforts to determine the mechanism of cell death in patients with LRRK2 mutations, the aetiology of LRRK2 PD is not well understood. To examine possible alterations in gene expression linked to the presence of LRRK2 mutations, we carried out a case versus control analysis of global gene expression in three systems: fibroblasts isolated from LRRK2 mutation carriers and healthy, non-mutation carrying controls; brain tissue from G2019S mutation carriers and controls; and HEK293 inducible LRRK2 wild type and mutant cell lines. No significant alteration in gene expression was found in these systems following correction for multiple testing. These data suggest that any alterations in basal gene expression in fibroblasts or cell lines containing mutations in LRRK2 are likely to be quantitatively small. This work suggests that LRRK2 is unlikely to play a direct role in modulation of gene expression, although it remains possible that this protein can influence mRNA expression under pathogenic cicumstances. PMID:21799870
Learning from M/EEG data with variable brain activation delays
Paris-Sud XI, Université de
the electromagnetic fields induced by brain activity. Typically, when collecting M/EEG data in neurosciences, the same- and electroencephalography (M/EEG) measure the electromagnetic signals produced by brain activity. In order to ad- dressLearning from M/EEG data with variable brain activation delays Wojciech Zaremba1,2 , M. Pawan Kumar
From the Cover: Reactivation of encoding-related brain activity during memory retrieval
Lars Nyberg; Reza Habib; Anthony R. McIntosh; Endel Tulving
Neuronal models predict that retrieval of specific event information reactivates brain regions that were active during encoding of this information. Consistent with this prediction, this positron-emission tomography study showed that remembering that visual words had been paired with sounds at encoding activated some of the auditory brain regions that were engaged during encoding. After word-sound encoding, activation of auditory brain
Beta-phenylethylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain.
Xie, Zhihua; Miller, Gregory M
Brain monoamines include common biogenic amines (dopamine, norepinephrine, and serotonin) and trace amines [beta-phenylethylamine (beta-PEA), tyramine, tryptamine, and octopamine]. Common biogenic amines are well established as neurotransmitters, but the roles and functional importance of trace amines remain elusive. Here, we re-evaluated the interaction of trace amines with trace amine-associated receptor 1 (TAAR1) and investigated effects of beta-PEA on monoamine transporter function and influence of monoamine autoreceptors on TAAR1 signaling. We confirmed that TAAR1 was activated by trace amines and demonstrated that TAAR1 activation by beta-PEA significantly inhibited uptake and induced efflux of [3H]dopamine, [3H]norepinephrine, and [3H]serotonin in transfected cells. In brain synaptosomes, beta-PEA significantly inhibited uptake and induced efflux of [3H]dopamine and [3H]serotonin in striatal and [3H]norepinephrine in thalamic synaptosomes of rhesus monkeys and wild-type mice, but it lacked the same effects in synaptosomes of TAAR1 knockout mice. The effect of beta-PEA on efflux was blocked by transporter inhibitors in either the transfected cells or wild-type mouse synaptosomes. We also demonstrated that TAAR1 signaling was not affected by monoamine autoreceptors at exposure to trace amines that we show to have poor binding affinity for the autoreceptors relative to common biogenic amines. These results reveal that beta-PEA alters monoamine transporter function via interacting with TAAR1 but not monoamine autoreceptors. The functional profile of beta-PEA may reveal a common mechanism by which trace amines exert modulatory effects on monoamine transporters in brain. PMID:18182557
Brain cholinesterase activity of apparently normal wild birds
Hill, E.F.
Organophosphorus and carbamate pesticides are potent anticholinesterase substances that have killed large numbers of wild birds of various species. Cause of death is diagnosed by demonstration of depressed brain cholinesterase (ChE) activity in combination with chemical detection of anticholinesterase residue in the affected specimen. ChE depression is determined by comparison of the affected specimen to normal ChE activity for a sample of control specimens of the same species, but timely procurement of controls is not always possible. Therefore, a reference file of normal whole brain ChE activity is provided for 48 species of wild birds from North America representing 11 orders and 23 families for use as emergency substitutes in diagnosis of anticholinesterase poisoning. The ChE values, based on 83 sets of wild control specimens from across the United States, are reproducible provided the described procedures are duplicated. Overall, whole brain ChE activity varied nearly three-fold among the 48 species represented, but it was usually similar for closely related species. However, some species were statistically separable in most families and some species of the same genus differed as much as 50%.
Altered gene expression in the brain and liver of female fathead minnows Pimephales promelas Rafinesque exposed to fadrozole
Villeneuve, Daniel L.; Knoebl, Iris; Larkin, Patrick; Miracle, Ann L.; Carter, Barbara J.; Denslow, Nancy D.; Ankley, Gerald T.
The fathead minnow (Pimephales promelas) is a small fish species widely used for ecotoxicology research and regulatory testing in North America. This study used a novel 2000 gene oligonucleotide microarray to evaluate the effects of the aromatase inhibitor, fadrozole, on gene expression in the liver and brain tissue of exposed females. Exposure to 60 ?g fadrozole/L for 7 d, resulted in the significant (p<0.05; high-moderate agreement among multiple probes spotted on the array) up-regulation of approximately 47 genes in brain and 188 in liver, and the significant down-regulation of 61 genes in brain and 162 in liver. In particular, fadrozole exposure elicited significant up-regulation of five genes in brain involved in the cholesterol synthesis pathway and altered the expression of over a dozen cytoskeleton-related genes. In the liver, there was notable down-regulation of genes coding for vitellogenin precursors, vigillin, and fibroin-like ovulatory proteins which were consistent with an expected reduction in plasma estradiol concentrations as a result of fadrozole exposure and an associated reduction in measured plasma vitellogenin concentrations. These changes coincided with a general down-regulation of genes coding for non-mitochondrial ribosomal proteins and proteins that play a role in translation. With the exception of the fibroin-like ovulatory proteins, real-time PCR results largely corroborated the microarray responses. Overall, results of this study demonstrate the utility of high density oligonucleotide microarrays for unsupervised, discovery-driven, ecotoxicogenomics research with the fathead minnow and helped inform the subsequent development of a 22,000 gene microarray for the species.
Quantitative Brain Electrical Activity in the Initial Screening of Mild Traumatic Brain Injuries
O'Neil, Brian; Prichep, Leslie S.; Naunheim, Roseanne; Chabot, Robert
Introduction: The incidence of emergency department (ED) visits for Traumatic Brain Injury (TBI) in the United States exceeds 1,000,000 cases/year with the vast majority classified as mild (mTBI). Using existing computed tomography (CT) decision rules for selecting patients to be referred for CT, such as the New Orleans Criteria (NOC), approximately 70% of those scanned are found to have a negative CT. This study investigates the use of quantified brain electrical activity to assess its possible role in the initial screening of ED mTBI patients as compared to NOC. Methods: We studied 119 patients who reported to the ED with mTBI and received a CT. Using a hand-held electroencephalogram (EEG) acquisition device, we collected data from frontal leads to determine the likelihood of a positive CT. The brain electrical activity was processed off-line to generate an index (TBI-Index, biomarker). This index was previously derived using an independent population, and the value found to be sensitive for significant brain dysfunction in TBI patients. We compared this performance of the TBI-Index to the NOC for accuracy in prediction of positive CT findings. Results: Both the brain electrical activity TBI-Index and the NOC had sensitivities, at 94.7% and 92.1% respectively. The specificity of the TBI-Index was more than twice that of NOC, 49.4% and 23.5% respectively. The positive predictive value, negative predictive value and the positive likelihood ratio were better with the TBI-Index. When either the TBI-Index or the NOC are positive (combining both indices) the sensitivity to detect a positive CT increases to 97%. Conclusion: The hand-held EEG device with a limited frontal montage is applicable to the ED environment and its performance was superior to that obtained using the New Orleans criteria. This study suggests a possible role for an index of brain function based on EEG to aid in the acute assessment of mTBI patients. PMID:23359586
Human brain activity with near-infrared spectroscopy
NASA Astrophysics Data System (ADS)
Luo, Qingming; Chance, Britton
Human brain activity was studied with a real time functional Near-InfraRed Imager (fNIRI). The imager has 16 measurement channels and covers 4 cm by 9 cm detection area. Brain activities in occipital, motor and prefrontal area were studied with the fNIRI. In prefrontal stimulation, language cognition, analogies, forming memory for new associations, emotional thinking, and mental arithmetic were carried out. Experimental results measured with fNIRI are demonstrated in this paper. It was shown that fNIRI technique is able to reveal the occipital activity during visual stimulation, and co-register well with results of fMRI in the motor cortex activity during finger tapping. In the studies of the effects of left prefrontal lobe on forming memory for new associations, it is shown that left prefrontal lobe activated more under deep conditions than that under shallow encoding, especially the dorsal part. In the studies of emotional thinking, it was shown that the responses were different between positive- negative emotional thinking and negative-positive emotional thinking. In mental arithmetic studies, higher activation was found in the first task than in the second, regardless of the difficulty, and higher activation was measured in subtraction of 17 than in subtraction of 3.
Functional interactions between intrinsic brain activity and behavior.
Sadaghiani, Sepideh; Kleinschmidt, Andreas
The brain continuously maintains a remarkably high level of intrinsic activity. This activity is non-stationary and its dynamics reveal highly structured patterns across several spatial scales, from fine-grained functional architecture in sensory cortices to large-scale networks. The mechanistic function of this activity is only poorly understood. The central goal of the current review is to provide an integrated summary of recent studies on structure, dynamics and behavioral consequences of spontaneous brain activity. In light of these empirical observations we propose that the structure of ongoing activity and its itinerant nature can be understood as an indispensible memory system modeling the statistical structure of the world. We review the dynamic properties of ongoing activity, and how they are malleable over short to long temporal scales that permit adapting over a range of short- to long-term cognitive challenges. We conclude by reviewing how the functional significance of ongoing activity manifests in its impact on human action, perception, and higher cognitive function. PMID:23643921
Methyl parathion activation by a partially purified rat brain fraction
Jaime Silva de Lima; Jayme da Cunha Bastos Neto; Vera Lucia Freire da Cunha Bastos; Julia Claro da Cunha; Flavia Franchini de Mattos Moraes; Maria de Fatima Alves Ferreira; Josino da Costa Moreira; Mauro Velho de Castro Faria
Organophosphorus pesticides are one of the most commonly used insecticide classes. They act through a potent inhibition of acetylcholinesterase (AChE). Many of them must undergo transformation into the corresponding oxon analogs to inhibit AChE. This study showed that a brain tissue subfraction transformed methyl parathion (O,O-dimethyl O-p-nitrophenyl phosphorothioate) in vitro. Methyl parathion activation was assayed by solvent extraction of the
Seizures, refractory status epilepticus, and depolarization block as endogenous brain activities
NASA Astrophysics Data System (ADS)
El Houssaini, Kenza; Ivanov, Anton I.; Bernard, Christophe; Jirsa, Viktor K.
Epilepsy, refractory status epilepticus, and depolarization block are pathological brain activities whose mechanisms are poorly understood. Using a generic mathematical model of seizure activity, we show that these activities coexist under certain conditions spanning the range of possible brain activities. We perform a detailed bifurcation analysis and predict strategies to escape from some of the pathological states. Experimental results using rodent data provide support of the model, highlighting the concept that these pathological activities belong to the endogenous repertoire of brain activities.
Metabolic Fingerprints of Altered Brain Growth, Osmoregulation and Neurotransmission in a Rett Syndrome Model
Angčle Viola; Véronique Saywell; Laurent Villard; Patrick J. Cozzone; Norbert W. Lutz; Mark Cookson
BackgroundRett syndrome (RS) is the leading cause of profound mental retardation of genetic origin in girls. Since RS is mostly caused by mutations in the MECP2 gene, transgenic animal models such as the Mecp2-deleted ("Mecp2-null") mouse have been employed to study neurological symptoms and brain function. However, an interdisciplinary approach drawing from chemistry, biology and neuroscience is needed to elucidate
Aims: Alcohol withdrawal-enhanced neurotoxicity contributes to the addictive process. Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity and learning. In this study, we explored the changes of serum BDNF levels in alcoholic patients at baseline and after one-week alcohol withdrawal. Methods:Twenty-five alcoholic patients were admitted for alcohol detoxification treatment, and 22 healthy control subjects were also enrolled.
Differential display detects host nucleic acid motifs altered in scrapie-infected brain.
Lathe, Richard; Harris, Alyson
The transmissible spongiform encephalopathies (TSEs) including scrapie have been attributed to an infectious protein or prion. Infectivity is allied to conversion of the endogenous nucleic-acid-binding protein PrP to an infectious modified form known as PrP(sc). The protein-only theory does not easily explain the enigmatic properties of the agent including strain variation. It was previously suggested that a short nucleic acid, perhaps host-encoded, might contribute to the pathoetiology of the TSEs. No candidate host molecules that might explain transmission of strain differences have yet been put forward. Differential display is a robust technique for detecting nucleic acid differences between two populations. We applied this technique to total nucleic acid preparations from scrapie-infected and control brain. Independent RNA preparations from eight normal and eight scrapie-infected (strain 263K) hamster brains were randomly amplified and visualized in parallel. Though the nucleic acid patterns were generally identical in scrapie-infected versus control brain, some rare bands were differentially displayed. Molecular species consistently overrepresented (or underrepresented) in all eight infected brain samples versus all eight controls were excised from the display, sequenced, and assembled into contigs. Only seven ros contigs (RNAs over- or underrepresented in scrapie) emerged, representing <4 kb from the transcriptome. All contained highly stable regions of secondary structure. The most abundant scrapie-only ros sequence was homologous to a repetitive transposable element (LINE; long interspersed nuclear element). Other ros sequences identified cellular RNA 7SL, clathrin heavy chain, visinin-like protein-1, and three highly specific subregions of ribosomal RNA (ros1-3). The ribosomal ros sequences accurately corresponded to LINE; retrotransposon insertion sites in ribosomal DNA (p<0.01). These differential motifs implicate specific host RNAs in the pathoetiology of the TSEs. PMID:19631225
Exploring altered consciousness states by magnetic resonance imaging in brain injury.
Lescot, Thomas; Galanaud, Damien; Puybasset, Louis
Traumatic brain injury (TBI) occurs abruptly, involves multiple specialized teams, calls on the health-care system in its emergency dimension, and engages the well-being of the patient and his relatives for a lifetime period. Clinicians in charge of these patients are faced with issues of uppermost importance: medical issues such as predicting the long-term neurological outcome of the comatose patient; ethical issues because of the influence of intensive care on the long-term survival of patients in a vegetative and minimally conscious state; legal issues because of the law that has set the concept of proportionality of care as the legal rule; and social issues as the result of the very high cost of these pathologies. Today's larger availability of magnetic resonance imaging (MRI) in ventilated patients and the recent improvements in hardware and in imaging techniques that have made the last-developed imaging techniques such as diffusion tensor imaging and magnetic resonance spectroscopy available in brain-trauma patients, are changing the paradigm in neurointensive care regarding outcome prediction. The old paradigm that no individual prognosis could be made at the subacute phase in TBI patients does not hold true anymore. This major change opens new challenging ethical questions. This review focuses on the brain explorations that are required, such as MRI, magnetic resonance spectroscopy, and diffusion tensor imaging, to provide the clinician with a multimodal assessment of the brain state to predict outcome of coma. Such an assessment will become mandatory in the near future to answer the crucial question of proportionality of care in these patients. PMID:19351357
Topiramate does not alter expression in rat brain of enzymes of arachidonic acid metabolism
Sandra Ghelardoni; Richard P. Bazinet; Stanley I. Rapoport; Francesca Bosetti
Rationale: When administered chronically to rats, drugs that are effective in bipolar disorder—lithium and the anticonvulsants, valproic acid and carbamazepine —have been shown to downregulate the expression of certain enzymes involved in brain arachidonic acid (AA) release and cyclooxygenase (COX)-mediated metabolism. Phase II clinical trials with the anticonvulsant topiramate (2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate) suggest that this drug may also be effective for
Maternal Deprivation Induces Depressive-like Behaviour and Alters Neurotrophin Levels in the Rat Brain
Gislaine Z. Réus; Roberto B. Stringari; Karine F. Ribeiro; Andreza L. Cipriano; Bruna S. Panizzutti; Laura Stertz; Camila Lersch; Flávio Kapczinski; Joăo Quevedo
The present study was aimed to evaluate the behavioral and molecular effects of maternal deprivation in adult rats. To this\\u000a aim, male rats deprived and non-deprived were assessed in the forced swimming and open-field tests in adult phase. In addition\\u000a adrenocorticotrophin hormone (ACTH) levels was assessed in serum and brain-derived-neurotrophic factor (BDNF), neurotrophin-3\\u000a (NT-3) and nerve growth factor (NGF) protein
Brain Iron, Transferrin and Ferritin Concentrations Are Altered in Developing Iron-Deficient Rats1
To study the iron, transferrin, and ferritin distribution at subcellular levels in response to acute dietary iron deficiency, we tested the hypothesis that early post-weaning iron deficiency can change iron and iron regulatory protein concentrations in rat brain. Male Sprague-Dawley rats were fed diets containing either 2 or 35 ng iron\\/g for 2, 3 or 4 wk starting at 21
Brain Activity of Adolescents with High Functioning Autism in Response to Emotional Words and Facial Emoticons
Han, Doug Hyun; Yoo, Hee Jeong; Kim, Bung Nyun; McMahon, William; Renshaw, Perry F.
Studies of social dysfunction in patients with autism spectrum disorder (ASD) have generally focused on the perception of emotional words and facial affect. Brain imaging studies have suggested that the fusiform gyrus is associated with both the comprehension of language and face recognition. We hypothesized that patients with ASD would have decreased ability to recognize affect via emotional words and facial emoticons, relative to healthy comparison subjects. In addition, we expected that this decreased ability would be associated with altered activity of the fusiform gyrus in patients with ASD. Ten male adolescents with ASDs and ten age and sex matched healthy comparison subjects were enrolled in this case-control study. The diagnosis of autism was further evaluated with the Autism Diagnostic Observation Schedule. Brain activity was assessed using functional magnetic resonance imaging (fMRI) in response to emotional words and facial emoticon presentation. Sixty emotional words (45 pleasant words +15 unpleasant words) were extracted from a report on Korean emotional terms and their underlying dimensions. Sixty emoticon faces (45 pleasant faces +15 unpleasant faces) were extracted and modified from on-line sites. Relative to healthy comparison subjects, patients with ASD have increased activation of fusiform gyrus in response to emotional aspects of words. In contrast, patients with ASD have decreased activation of fusiform gyrus in response to facial emoticons, relative to healthy comparison subjects. We suggest that patients with ASD are more familiar with word descriptions than facial expression as depictions of emotion. PMID:24621866
The transliminal brain at rest: baseline EEG, unusual experiences, and access to unconscious mental activity.
Fleck, Jessica I; Green, Deborah L; Stevenson, Jennifer L; Payne, Lisa; Bowden, Edward M; Jung-Beeman, Mark; Kounios, John
Transliminality reflects individual differences in the threshold at which unconscious processes or external stimuli enter into consciousness. Individuals high in transliminality possess characteristics such as magical ideation, belief in the paranormal, and creative personality traits, and also report the occurrence of manic/mystic experiences. The goal of the present research was to determine if resting brain activity differs for individuals high versus low in transliminality. We compared baseline EEG recordings (eyes-closed) between individuals high versus low in transliminality, assessed using The Revised Transliminality Scale of Lange et al. (2000). Identifying reliable differences at rest between high- and low-transliminality individuals would support a predisposition for transliminality-related traits. Individuals high in transliminality exhibited lower alpha, beta, and gamma power than individuals low in transliminality over left posterior association cortex and lower high alpha, low beta, and gamma power over the right superior temporal region. In contrast, when compared to individuals low in transliminality, individuals high in transliminality exhibited greater gamma power over the frontal-midline region. These results are consistent with prior research reporting reductions in left temporal/parietal activity, as well as the desynchronization of right temporal activity in schizotypy and related schizophrenia spectrum disorders. Further, differences between high- and low-transliminality groups extend existing theories linking altered hemispheric asymmetries in brain activity to a predisposition toward schizophrenia, paranormal beliefs, and unusual experiences. PMID:18814870
Brain activation of the defensive and appetitive survival systems in obsessive compulsive disorder.
Gonçalves, Óscar F; Soares, José Miguel; Carvalho, Sandra; Leite, Jorge; Ganho, Ana; Fernandes-Gonçalves, Ana; Frank, Brandon; Pocinho, Fernando; Relvas, Joăo; Carracedo, Angel; Sampaio, Adriana
Several studies have shown that basic emotions are responsible for a significant enhancement of early visual processes and increased activation in visual processing brain regions. It may be possible that the cognitive uncertainty and repeated behavioral checking evident in Obsessive Compulsive Disorder (OCD) is due to the existence of abnormalities in basic survival circuits, particularly those associated with the visual processing of the physical characteristics of emotional-laden stimuli. The objective of the present study was to test if patients with OCD show evidence of altered basic survival circuits, particularly those associated with the visual processing of the physical characteristics of emotional stimuli. Fifteen patients with OCD and 12 healthy controls underwent functional magnetic resonance imaging acquisition while being exposed to emotional pictures, with different levels of arousal, intended to trigger the defensive and appetitive basic survival circuits. Overall, the present results seem to indicate dissociation in the activity of the defense and appetitive survival systems in OCD. Results suggest that the clinical group reacts to basic threat with a strong activation of the defensive system mobilizing widespread brain networks (i.e., frontal, temporal, occipital-parietal, and subcortical nucleus) and blocking the activation of the appetitive system when facing positive emotional triggers from the initial stages of visual processing (i.e., superior occipital gyrus). PMID:24760279
Abnormal autonomic and associated brain activities during rest in autism spectrum disorder.
Eilam-Stock, Tehila; Xu, Pengfei; Cao, Miao; Gu, Xiaosi; Van Dam, Nicholas T; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Park, Yunsoo; Siller, Michael; He, Yong; Hof, Patrick R; Fan, Jin
Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition. PMID:24424916
Polygenic risk for schizophrenia associated with working memory-related prefrontal brain activation in patients with schizophrenia and healthy controls.
Kauppi, Karolina; Westlye, Lars T; Tesli, Martin; Bettella, Francesco; Brandt, Christine L; Mattingsdal, Morten; Ueland, Torill; Espeseth, Thomas; Agartz, Ingrid; Melle, Ingrid; Djurovic, Srdjan; Andreassen, Ole A
Schizophrenia is a highly heritable and polygenic disease, and identified common genetic variants have shown weak individual effects. Many studies have reported altered working memory (WM)-related brain activation in schizophrenia, preferentially in the frontal lobe. Such differences in brain activations could reflect inherited alterations possibly involved in the disease etiology, or rather secondary disease-related mechanisms. The use of polygenic risk scores (PGRS) based on a large number of risk polymorphisms with small effects is a valuable approach to examine the effect of cumulative genetic risk on brain functioning. This study examined the impact of cumulative genetic risk for schizophrenia on WM-related brain activations, assessed with functional magnetic resonance imaging. For each participant (63 schizophrenia patients and 118 healthy controls), we calculated a PGRS for schizophrenia based on 18 862 single-nucleotide polymorphism in a large multicenter genome-wide association study including 9146 schizophrenia patients and 12 111 controls, performed by the Psychiatric Genomics Consortium. As expected, the PGRS was significantly higher in patients compared with healthy controls. Further, the PGRS was related to differences in frontal lobe brain activation between high and low WM demand. Specifically, even in absence of main effects of diagnosis, increased PGRS was associated with decreased activation difference in the right middle-superior prefrontal cortex (BA 10/11) and the right inferior frontal gyrus (BA 45). This effect was seen in both cases and controls, and was not influenced by sex, age, or task performance. The findings support the notion of dysregulation of frontal lobe functioning as an inherited vulnerability factor in schizophrenia. PMID:25392519
Early Oxygen-Utilization and Brain Activity in Preterm Infants
de Vries, Linda S.; Groenendaal, Floris; Toet, Mona C.; Lemmers, Petra M. A.; Vosse van de, Renč E.; van Bel, Frank; Benders, Manon J. N. L.
The combined monitoring of oxygen supply and delivery using Near-InfraRed spectroscopy (NIRS) and cerebral activity using amplitude-integrated EEG (aEEG) could yield new insights into brain metabolism and detect potentially vulnerable conditions soon after birth. The relationship between NIRS and quantitative aEEG/EEG parameters has not yet been investigated. Our aim was to study the association between oxygen utilization during the first 6 h after birth and simultaneously continuously monitored brain activity measured by aEEG/EEG. Forty-four hemodynamically stable babies with a GA < 28 weeks, with good quality NIRS and aEEG/EEG data available and who did not receive morphine were included in the study. aEEG and NIRS monitoring started at NICU admission. The relation between regional cerebral oxygen saturation (rScO2) and cerebral fractional tissue oxygen extraction (cFTOE), and quantitative measurements of brain activity such as number of spontaneous activity transients (SAT) per minute (SAT rate), the interval in seconds (i.e. time) between SATs (ISI) and the minimum amplitude of the EEG in ?V (min aEEG) were evaluated. rScO2 was negatively associated with SAT rate (?=-3.45 [CI=-5.76- -1.15], p=0.004) and positively associated with ISI (?=1.45 [CI=0.44-2.45], p=0.006). cFTOE was positively associated with SAT rate (?=0.034 [CI=0.009-0.059], p=0.008) and negatively associated with ISI (?=-0.015 [CI=-0.026- -0.004], p=0.007). Oxygen delivery and utilization, as indicated by rScO2 and cFTOE, are directly related to functional brain activity, expressed by SAT rate and ISI during the first hours after birth, showing an increase in oxygen extraction in preterm infants with increased early electro-cerebral activity. NIRS monitored oxygenation may be a useful biomarker of brain vulnerability in high-risk infants. PMID:25965343
Brain catalase activity is highly correlated with ethanol-induced locomotor activity in mice.
Correa, M; Sanchis-Segura, C; Aragon, C M
It has been demonstrated that acute administration of lead to mice enhances brain catalase activity and ethanol-induced locomotion. These effects of lead seem to be related, since they show similar time courses and occur at similar doses. In the present study, in an attempt to further evaluate the relation between brain catalase activity and lead-induced changes in ethanol-stimulated locomotion, the interaction between lead acetate and 3-amino-1H,2,4-triazole (AT), a well-known catalase inhibitor, was assessed. In this study, lead acetate or saline was acutely injected intraperitoneally to Swiss mice at doses of 50 or 100 mg/kg 7 days before testing. On the test day, animals received an intraperitoneal injection of AT (0, 10, or 500 mg/kg). Five hours following AT treatment, ethanol (0.0 or 2.5 g/kg, ip) was injected and the animals were placed in open-field chambers, in which locomotion was measured for 10 min. Neither lead exposure nor AT administration, either alone or in combination, had any effect on spontaneous locomotor activity. AT treatment reduced ethanol-induced locomotion as well as brain catalase activity. On the other hand, ambulation and brain catalase activity were significantly increased by both doses of lead. Furthermore, AT significantly reduced the potentiation produced by lead acetate on brain catalase and on ethanol-induced locomotor activity in a dose-dependent manner. A significant correlation was found between locomotion and catalase activity across all test conditions. The results show that brain catalase activity is involved in the effects of lead acetate on ethanol-induced locomotion in mice. Thus, this study confirms the notion that brain catalase provides the molecular basis for understanding some of the mechanisms of the action of ethanol in the central nervous system. PMID:11495670
Genetic activation of mTORC1 signaling worsens neurocognitive outcome after traumatic brain injury.
Rozas, Natalia S; Redell, John B; Hill, Julia L; McKenna, James; Moore, Anthony N; Gambello, Michael J; Dash, Pramod K
Although the mechanisms that contribute to the development of traumatic brain injury (TBI)-related deficits are not fully understood, it has been proposed that altered energy utilization may be a contributing factor. The tuberous sclerosis complex, a heterodimer composed of hamartin/Tsc-1 and tuberin/Tsc-2, is a critical regulatory node that integrates nutritional and growth signals to govern energy using processes by regulating the activity of mechanistic Target of Rapamycin complex 1 (mTORC1). mTORC1 activation results in enhanced protein synthesis, an energy consuming process. We show that mice that have a heterozygous deletion of Tsc2 exhibit elevated basal mTORC1 activity in the cortex and the hippocampus while still exhibiting normal motor and neurocognitive functions. In addition, a mild closed head injury (mCHI) that did not activate mTORC1 in wild-type mice resulted in a further increase in mTORC1 activity in Tsc2(+/KO) mice above the level of activity observed in uninjured Tsc2(+/KO) mice. This enhanced level of increased mTORC1 activity was associated with worsened cognitive function as assessed using the Morris water maze and context discrimination tasks. These results suggest that there is a threshold of increased mTORC1 activity after a TBI that is detrimental to neurobehavioral performance, and interventions to inhibit excessive mTORC1 activation may be beneficial to neurocognitive outcome. PMID:25025304
Pyrithiamine-induced thiamine deficiency alters proliferation and neurogenesis in both neurogenic and vulnerable areas of the rat brain.
Hazell, Alan S; Wang, Dongmei; Oanea, Raluca; Sun, Simon; Aghourian, Meghmik; Yong, Jee Jung
Thiamine deficiency (TD) leads to Wernicke's encephalopathy (WE), in which focal histological lesions occur in periventricular areas of the brain. Recently, impaired neurogenesis has been reported in the hippocampus during the dietary form of TD, and in pyrithiamine-induced TD (PTD), a well-characterized model of WE. To further characterize the consequences of PTD on neural stem/progenitor cell (NSPC) activity, we have examined the effect of this treatment in the rat on both the subventricular zone (SVZ) of the rostral lateral ventricle and subgranular layer (SGL) of the hippocampus, and in the thalamus and inferior colliculus, two vulnerable brain regions in this disorder. In both the SVZ and SGL, PTD led to a decrease in the numbers of bromodeoxyuridine-stained cells, indicating that proliferation of NSPCs destined for neurogenesis in these areas was reduced. Doublecortin (DCX) immunostaining in the SGL was decreased, indicating a reduction in neuroblast formation, consistent with impaired NSPC activity. DCX labeling was not apparent in focal areas of vulnerability. In the thalamus, proliferation of cells was absent while in the inferior colliculus, numerous actively dividing cells were apparent, indicative of a differential response between these two brain regions. Exposure of cultured neurospheres to PTD resulted in decreased proliferation of NSPCs, consistent with our in vivo findings. Together, these results indicate that PTD considerably affects cell proliferation and neurogenesis activity in both neurogenic areas and parts of the brain known to display structural and functional vulnerability, confirming and extending recent findings on the effects of TD on neurogenesis. Future use of NSPCs in vitro may allow a closer and more detailed examination of the mechanism(s) underlying inhibition of these cells during TD. PMID:24078061
Altered Muscarinic Acetylcholine Receptor Subtype Binding in Neonatal Rat Brain following Exposure to Chlorpyrifos or Methyl Parathion
Shirley X. Guo-Ross; Janice E. Chambers; Edward C. Meek; Russell L. Carr
The neurodevelopmental effects of two organophosphorus (OP) insecticides, chlorpyrifos (CPS) and methyl parathion (MPS), on cholinesterase (ChE) activity and muscarinic acetylcholine re- ceptor (mAChR) binding were investigated in neonatal rat brain. Animals were orally gavaged using an incremental dosing regimen from postnatal day 1 (PND1) until PND8 with a low, medium, and high dosage for both CPS and MPS. On
Genetic alterations associated with the evolution and progression of astrocytic brain tumours
H. Ohgaki; P. Kleihues; B. Schäuble; A. Hausen; K. Ammon
Diffusely infiltrating low-grade astrocytomas (WHO grade II) have an intrinsic tendency for progression to anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV). This change is due to the sequential acquisition of genetic alterations, several of which have recently been identified. In low-grade astrocytomas, p53 mutations with or without loss of heterozygosity on chromosome 17p are the principal detectable
Brain alteration in a Nude\\/SCID fetus carrying FOXN1 homozygous mutation
Stefania Amorosi; Ilaria Vigliano; Ennio Del Giudice; Luigi Panico; Giuseppe M. Maruotti; Anna Fusco; Mario Quarantelli; Carla Ciccone; Matilde V. Ursini; Pasquale Martinelli; Claudio Pignata
A critical role of the FOX transcription factors in the development of different tissues has been shown. Among these genes, FOXN1 encodes a protein whose alteration is responsible for the Nude\\/SCID phenotype. Recently, our group reported on a human Nude\\/SCID fetus, which also had severe neural tube defects, namely anencephaly and spina bifida. This led to hypothesize that FOXN1 could
Compounds from Silicones Alter Enzyme Activity in Curing Barnacle Glue and Model Enzymes
Rittschof, Daniel; Orihuela, Beatriz; Harder, Tilmann; Stafslien, Shane; Chisholm, Bret; Dickinson, Gary H.
Background Attachment strength of fouling organisms on silicone coatings is low. We hypothesized that low attachment strength on silicones is, in part, due to the interaction of surface available components with natural glues. Components could alter curing of glues through bulk changes or specifically through altered enzyme activity. Methodology/Principal Findings GC-MS analysis of silicone coatings showed surface-available siloxanes when the coatings were gently rubbed with a cotton swab for 15 seconds or given a 30 second rinse with methanol. Mixtures of compounds were found on 2 commercial and 8 model silicone coatings. The hypothesis that silicone components alter glue curing enzymes was tested with curing barnacle glue and with commercial enzymes. In our model, barnacle glue curing involves trypsin-like serine protease(s), which activate enzymes and structural proteins, and a transglutaminase which cross-links glue proteins. Transglutaminase activity was significantly altered upon exposure of curing glue from individual barnacles to silicone eluates. Activity of purified trypsin and, to a greater extent, transglutaminase was significantly altered by relevant concentrations of silicone polymer constituents. Conclusions/Significance Surface-associated silicone compounds can disrupt glue curing and alter enzyme properties. Altered curing of natural glues has potential in fouling management. PMID:21379573
Altered local field potential activity and serotonergic neurotransmission are further characteristics of the Flinders sensitive line rat model of depression.
Voget, Mareike; Rummel, Julia; Avchalumov, Yosef; Sohr, Reinhard; Haumesser, Jens K; Rea, Ellis; Mathé, Aleksander A; Hadar, Ravit; van Riesen, Christoph; Winter, Christine
A significant portion of patients suffering from major depression remains refractory to available antidepressant treatment strategies. This highlights the need for a better understanding of the underlying neuropathology in order to develop rationale-based treatments. Here we aimed to further characterize neurobiological abnormalities of the Flinders Sensitive Line (FSL) rat model of depression. Biochemically, in FSL rats we mainly found increased levels of serotonin in most cortical and subcortical brain regions when compared to controls. Using electrophysiological measurements, in FSL rats we found decreased alpha, beta and low gamma oscillatory activity in the medial prefrontal cortex and nucleus accumbens and decreased alpha and beta as well as increased low gamma oscillatory activity in the subthalamicus nucleus when compared to controls. In summary, we show distinct neurochemical properties in combination with particular oscillatory activity patterns for brain areas thought to be pathophysiologically relevant for depression. Our data contribute to the further understanding of neurobiological alterations in the FSL rat model of depression that could provide a basis for research into future therapeutic strategies. PMID:26025511
Training-induced improvements in postural control are accompanied by alterations in cerebellar white matter in brain injured patients.
Drijkoningen, David; Caeyenberghs, Karen; Leunissen, Inge; Vander Linden, Catharine; Leemans, Alexander; Sunaert, Stefan; Duysens, Jacques; Swinnen, Stephan P
We investigated whether balance control in young TBI patients can be promoted by an 8-week balance training program and whether this is associated with neuroplastic alterations in brain structure. The cerebellum and cerebellar peduncles were selected as regions of interest because of their importance in postural control as well as their vulnerability to brain injury. Young patients with moderate to severe TBI and typically developing (TD) subjects participated in balance training using PC-based portable balancers with storage of training data and real-time visual feedback. An additional control group of TD subjects did not attend balance training. Mean diffusivity and fractional anisotropy were determined with diffusion MRI scans and were acquired before, during (4 weeks) and at completion of training (8 weeks) together with balance assessments on the EquiTest® System (NeuroCom) which included the Sensory Organization Test, Rhythmic Weight Shift and Limits of Stability protocols. Following training, TBI patients showed significant improvements on all EquiTest protocols, as well as a significant increase in mean diffusivity in the inferior cerebellar peduncle. Moreover, in both training groups, diffusion metrics in the cerebellum and/or cerebellar peduncles at baseline were predictive of the amount of performance increase after training. Finally, amount of training-induced improvement on the Rhythmic Weight Shift test in TBI patients was positively correlated with amount of change in fractional anisotropy in the inferior cerebellar peduncle. This suggests that training-induced plastic changes in balance control are associated with alterations in the cerebellar white matter microstructure in TBI patients. PMID:25610786
Training-induced improvements in postural control are accompanied by alterations in cerebellar white matter in brain injured patients
Drijkoningen, David; Caeyenberghs, Karen; Leunissen, Inge; Vander Linden, Catharine; Leemans, Alexander; Sunaert, Stefan; Duysens, Jacques; Swinnen, Stephan P.
We investigated whether balance control in young TBI patients can be promoted by an 8-week balance training program and whether this is associated with neuroplastic alterations in brain structure. The cerebellum and cerebellar peduncles were selected as regions of interest because of their importance in postural control as well as their vulnerability to brain injury. Young patients with moderate to severe TBI and typically developing (TD) subjects participated in balance training using PC-based portable balancers with storage of training data and real-time visual feedback. An additional control group of TD subjects did not attend balance training. Mean diffusivity and fractional anisotropy were determined with diffusion MRI scans and were acquired before, during (4 weeks) and at completion of training (8 weeks) together with balance assessments on the EquiTest® System (NeuroCom) which included the Sensory Organization Test, Rhythmic Weight Shift and Limits of Stability protocols. Following training, TBI patients showed significant improvements on all EquiTest protocols, as well as a significant increase in mean diffusivity in the inferior cerebellar peduncle. Moreover, in both training groups, diffusion metrics in the cerebellum and/or cerebellar peduncles at baseline were predictive of the amount of performance increase after training. Finally, amount of training-induced improvement on the Rhythmic Weight Shift test in TBI patients was positively correlated with amount of change in fractional anisotropy in the inferior cerebellar peduncle. This suggests that training-induced plastic changes in balance control are associated with alterations in the cerebellar white matter microstructure in TBI patients. PMID:25610786
Protein expression of targets of the FMRP regulon is altered in brains of subjects with schizophrenia and mood disorders.
Folsom, Timothy D; Thuras, Paul D; Fatemi, S Hossein
Fragile X mental retardation protein (FMRP) is an RNA binding protein with 842 target mRNAs in mammalian brain. Silencing of the fragile X mental retardation 1 (FMR1) gene leads to loss of expression of FMRP and upregulated metabotropic glutamate receptor 5 (mGluR5) signaling resulting in the multiple physical and cognitive deficits associated with fragile X syndrome (FXS). Reduced FMRP expression has been identified in subjects with autism, schizophrenia, bipolar disorder, and major depression who do not carry the mutation for FMR1. Our laboratory has recently demonstrated altered expression of four downstream targets of FMRP-mGluR5 signaling in brains of subjects with autism: homer 1, amyloid beta A4 precursor protein (APP), ras-related C3 botulinum toxin substrate 1 (RAC1), and striatal-enriched protein tyrosine phosphatase (STEP). In the current study we investigated the expression of the same four proteins in lateral cerebella of subjects with schizophrenia, bipolar disorder, and major depression and in frontal cortex of subjects with schizophrenia and bipolar disorder. In frontal cortex we observed: 1) reduced expression of 120kDa form of APP in subjects with schizophrenia and bipolar disorder; 2) reduced expression of 61kDa and 33kDa forms of STEP in subjects with schizophrenia; 3) reduced expression of 88kDa form of APP in subjects with bipolar disorder; and 3) trends for reduced expression of 88kDa form of APP and homer 1 in subjects with schizophrenia and bipolar disorder, respectively. In lateral cerebella there was no group difference, however we observed increased expression of RAC1 in subjects with bipolar disorder, and trends for increased RAC1 in subjects with schizophrenia and major depression. Our results provide further evidence that proteins involved in the FMRP-mGluR5 signaling pathway are altered in schizophrenia and mood disorders. PMID:25956630
Altered expression of brain monocarboxylate transporter 1 in models of temporal lobe epilepsy.
Lauritzen, Fredrik; Perez, Edgar L; Melillo, Eric R; Roh, Jung-Min; Zaveri, Hitten P; Lee, Tih-Shih W; Wang, Yue; Bergersen, Linda H; Eid, Tore
Monocarboxylate transporter 1 (MCT1) facilitates the transport of monocarboxylate fuels (lactate, pyruvate and ketone bodies) and acidic drugs, such as valproic acid, across cell membranes. We recently reported that MCT1 is deficient on microvessels in the epileptogenic hippocampal formation in patients with medication-refractory temporal lobe epilepsy (TLE). To further define the role of MCT1 in the pathophysiology of TLE, we used immunohistochemistry and stereological analysis to localize and quantify the transporter in the hippocampal formation in three novel and highly relevant rat models of TLE and in nonepileptic control animals. One model utilizes methionine sulfoximine to induce brain glutamine synthetase deficiency and recurrent limbic seizures, while two models employ an episode of perforant pathway stimulation to cause epilepsy. MCT1 was lost on microvessels and upregulated on astrocytes in the hippocampal formation in all models of TLE. Notably, the loss of MCT1 on microvessels was not due to a reduction in microvessel density. The similarities in MCT1 expression among human subjects with TLE and several animal models of the disease strongly suggest a critical role of this molecule in the pathogenesis of TLE. We hypothesize that the downregulation of MCT1 may promote seizures via impaired uptake of ketone bodies and antiepileptic drugs by the epileptogenic brain. We also propose that the overexpression of MCT1 on astrocytes may lead to increased uptake or release of monocarboxylates by these cells, with important implications for brain metabolism and excitability. These hypotheses can now be rigorously tested in several animal models that replicate key features of human TLE. PMID:21856423
Altered Expression of Brain Monocarboxylate Transporter 1 in Models of Temporal Lobe Epilepsy
Lauritzen, Fredrik; Perez, Edgar L.; Melillo, Eric R.; Roh, Jung-Min; Zaveri, Hitten P.; Lee, Tih-Shih W.; Wang, Yue; Bergersen, Linda H.; Eid, Tore
Monocarboxylate transporter 1 (MCT1) facilitates the transport of monocarboxylate fuels (lactate, pyruvate and ketone bodies) and acidic drugs, such as valproic acid, across cell membranes. We recently reported that MCT1 is deficient on microvessels in the epileptogenic hippocampal formation in patients with medication-refractory temporal lobe epilepsy (TLE). To further define the role of MCT1 in the pathophysiology of TLE, we used immunohistochemistry and stereological analysis to localize and quantify the transporter in the hippocampal formation in three novel and highly relevant rat models of TLE and in nonepileptic control animals. One model utilizes methionine sulfoximine to induce brain glutamine synthetase deficiency and recurrent limbic seizures, while two models employ an episode of perforant pathway stimulation to cause epilepsy. MCT1 was lost on microvessels and upregulated on astrocytes in the hippocampal formation in all models of TLE. Notably, the loss of MCT1 on microvessels was not due to a reduction in microvessel density. The similarities in MCT1 expression among human subjects with TLE and several animal models of the disease strongly suggest a critical role of this molecule in the pathogenesis of TLE. We hypothesize that the downregulation of MCT1 may promote seizures via impaired uptake of ketone bodies and antiepileptic drugs by the epileptogenic brain. We also propose that the overexpression of MCT1 on astrocytes may lead to increased uptake or release of monocarboxylates by these cells, with important implications for brain metabolism and excitability. These hypotheses can now be rigorously tested in several animal models that replicate key features of human TLE. PMID:21856423
Expertise in folk music alters the brain processing of Western harmony.
Tervaniemi, M; Tupala, T; Brattico, E
In various paradigms of modern neurosciences of music, experts of Western classical music have displayed superior brain architecture when compared with individuals without explicit training in music. In this paper, we show that chord violations embedded in musical cadences were neurally processed in a facilitated manner also by musicians trained in Finnish folk music. This result, obtained by using early right anterior negativity (ERAN) as an index of harmony processing, suggests that tonal processing is advanced in folk musicians by their long-term exposure to both Western and non-Western music. PMID:22524352
Fast 3D Brain Segmentation Using Dual-Front Active Contours with Optional User-Interaction
Cohen, Laurent
Fast 3D Brain Segmentation Using Dual-Front Active Contours with Optional User-Interaction Hua Li1 attributes of 3D brain segmentation algorithms in- clude robustness, accuracy, computational efficiency result. We propose a novel 3D brain cortex segmentation procedure utilizing dual- front active contours
Mapping brain activity at scale with cluster computing.
Freeman, Jeremy; Vladimirov, Nikita; Kawashima, Takashi; Mu, Yu; Sofroniew, Nicholas J; Bennett, Davis V; Rosen, Joshua; Yang, Chao-Tsung; Looger, Loren L; Ahrens, Misha B
Understanding brain function requires monitoring and interpreting the activity of large networks of neurons during behavior. Advances in recording technology are greatly increasing the size and complexity of neural data. Analyzing such data will pose a fundamental bottleneck for neuroscience. We present a library of analytical tools called Thunder built on the open-source Apache Spark platform for large-scale distributed computing. The library implements a variety of univariate and multivariate analyses with a modular, extendable structure well-suited to interactive exploration and analysis development. We demonstrate how these analyses find structure in large-scale neural data, including whole-brain light-sheet imaging data from fictively behaving larval zebrafish, and two-photon imaging data from behaving mouse. The analyses relate neuronal responses to sensory input and behavior, run in minutes or less and can be used on a private cluster or in the cloud. Our open-source framework thus holds promise for turning brain activity mapping efforts into biological insights. PMID:25068736
Wistar Audiogenic Rats (WAR) exhibit altered levels of cytokines and brain-derived neurotrophic factor following audiogenic seizures.
de Souza Bernardino, Túlio Cezar; Teixeira, Antonio Lúcio; Miranda, Aline Silva; Guidine, Patrícia Maia; Rezende, Gustavo; Doretto, Maria Carolina; Castro, Gabriel Perfeito; Drummond, Luciana; Moraes, Márcio Flávio Dutra; Tito, Pedro Augusto Lopes; de Oliveira, Antonio Carlos Pinheiro; Reis, Helton José
Increasing body of evidence suggests that inflammatory and neurotrophic factors might be important for epileptogenesis. Most animal studies demonstrated altered levels of these mediators in drug-induced models of seizures and epilepsy. In the present study, we investigated the production of cytokines and a neurotrophin in the brain of Wistar Audiogenic Rats (WAR), a genetic model of epilepsy, stimulated with high-intensity sound. Four hours after stimulation, animals were decapitated and the hippocampus, inferior colliculus, striatum and cortex were removed for evaluation of the levels of interleukin (IL)-1?, IL-6, tumor necrosis factor (TNF)-? and brain derived neurotrophic factor (BDNF). All the cytokines and BDNF levels were increased in the cortex. Increased levels of TNF-? and IL-6 were also observed in the striatum. Finally, TNF-? also increased in the inferior colliculus after the seizures induced by high-intensity sound. Although different studies have demonstrated that the levels of cytokines and BDNF increase in animal models of epilepsy induced by chemical stimuli, we provided here evidence that these mediators are also increased in WAR, a genetic model of epilepsy. Thus, the observed increase in these mediators might be involved in the pathophysiology of epilepsy. PMID:25936592
P-glycoprotein alters blood–brain barrier penetration of antiepileptic drugs in rats with medically intractable epilepsy
Ma, Aimei; Wang, Cuicui; Chen, Yinghui; Yuan, Weien
P-glycoprotein is one of the earliest known multidrug transporters and plays an important role in resistance to chemotherapeutic drugs. In this study, we detected levels of P-glycoprotein and its mRNA expression in a rat brain model of medically intractable epilepsy established by amygdala kindling and drug selection. We investigated whether inhibition of P-glycoprotein affects the concentration of antiepileptic drugs in cortical extracellular fluid. We found that levels of P-glycoprotein and its mRNA expression were upregulated in epileptic cerebral tissue compared with cerebral tissue from normal rats. The concentrations of two antiepileptic drugs, carbamazepine and phenytoin, were very low in the cortical extracellular fluid of rats with medically intractable epilepsy, and were restored after blockade of P-glycoprotein by verapamil. These results show that increased P-glycoprotein levels alter the ability of carbamazepine and phenytoin to penetrate the blood–brain barrier and reduce the concentrations of these agents in extracellular cortical fluid. High P-glycoprotein levels may be involved in resistance to antiepileptic drugs in medically intractable epilepsy. PMID:24348021
Alteration of limb and brain patterning in early mouse embryos by ultrasound-guided injection of Shh-expressing cells.
Liu, A; Joyner, A L; Turnbull, D H
A basic limitation of the study of development in the mouse is the inaccessibility of the embryos, which are encased in the maternal uterus. We demonstrate the first use of ultrasound backscatter microscopy for guiding injections of cells and other agents into early stage mouse embryos. Cells were injected into the mouse neural tube cavity as early as 9.5 days post coitus (E9.5), and into the developing limb buds as early as E10.5. Furthermore, a cell-line engineered to express the secreted factor Sonic Hedgehog (Shh) was injected into early developing mouse brains or limbs. The Shh-expressing cells were found to induce ectopic expression of the Shh target genes Patched and Hnf3beta in the dorsal brain, and to alter digit patterning in the anterior limb bud. These results show that gene misexpression studies can be performed in mouse embryos using ultrasound-guided injection of transfected cells or retroviruses. In combination with the many available mouse mutants, this method offers a new approach for analyzing genetic interactions through gain-of-function studies performed in mutant mouse backgrounds. PMID:9739117
Source localization of brain activity using helium-free interferometer
Dammers, Jürgen, E-mail: email@example.com; Chocholacs, Harald; Eich, Eberhard; Boers, Frank [Institute of Neuroscience and Medicine (INM-4), Forschungszentrum Jülich, Jülich (Germany); Faley, Michael; Dunin-Borkowski, Rafal E. [Peter Grünberg Institute (PGI-5), Forschungszentrum Jülich, Jülich (Germany); Jon Shah, N. [Institute of Neuroscience and Medicine (INM-4), Forschungszentrum Jülich, Jülich (Germany); Department of Neurology, RWTH Aachen University, Aachen (Germany); Jülich Aachen Research Alliance (JARA)—Translational Brain Medicine, Jülich (Germany)
To detect extremely small magnetic fields generated by the human brain, currently all commercial magnetoencephalography (MEG) systems are equipped with low-temperature (low-T{sub c}) superconducting quantum interference device (SQUID) sensors that use liquid helium for cooling. The limited and increasingly expensive supply of helium, which has seen dramatic price increases recently, has become a real problem for such systems and the situation shows no signs of abating. MEG research in the long run is now endangered. In this study, we report a MEG source localization utilizing a single, highly sensitive SQUID cooled with liquid nitrogen only. Our findings confirm that localization of neuromagnetic activity is indeed possible using high-T{sub c} SQUIDs. We believe that our findings secure the future of this exquisitely sensitive technique and have major implications for brain research and the developments of cost-effective multi-channel, high-T{sub c} SQUID-based MEG systems.
Alterations in brain structures underlying language function in young adults at high familial risk for schizophrenia
Francis, Alan N.; Seidman, Larry J.; Jabbar, Gul A.; Mesholam-Gately, Raquelle; Thermenos, Heidi W.; Juelich, Richard; Proal, Ashley C.; Shenton, Martha; Kubicki, Marek; Mathew, Ian; Keshavan, Matcheri; DeLisi, Lynn E.
Introduction Neuroanatomical and cognitive alterations typical of schizophrenia (SZ) patients are observed to a lesser extent in their adolescent and adult first-degree relatives, likely reflecting neurodevelopmental abnormalities associated with genetic risk for the illness. The anatomical pathways for language are hypothesized to be abnormal and to underlie the positive symptoms of schizophrenia. Examining non-psychotic relatives at high familial risk (FHR) for schizophrenia may clarify if these deficits represent trait markers associated with genetic vulnerability, rather than specific markers resulting from the pathological process underlying schizophrenia. Methods T1 MRI scans from a 3T Siemens scanner of young adult FHR subjects (N=46) and controls with no family history of illness (i.e. at low genetic risk LRC; N=31) were processed using FreeSurfer 5.0. We explored volumetric and lateralization alterations in regions associated with language processing. An extensive neuropsychological battery of language measures was administered. Results No significant differences were observed between groups on any language measures. Controlling Intracranial volume, significantly smaller center Pars Triangularis (PT) (p<0.01) and right Pars Orbitalis (PO) (p < 0.01) volumes and reversal of the L > R Pars Orbitalis (p < 0.001) lateralization were observed in FHR subjects. In addition, the L Pars Triangularis and R Pars Orbitalis correlated with performance on tests of linguistic function in the FHR group. Conclusions Reduced volume and reversed structural asymmetry in language-related regions hypothesized to be altered in SZ are also found in first degree relatives at FHR, despite normal language performance. To clarify if these findings are endophenotypes for Sz, future studied would need to be performed of ill and well family members no longer within the age range of risk for illness to show these deficits segregate with schizophrenia within families. Moreover, measures of complex language need to be studied to determine if FHR individuals manifest impairments in some aspects of language function. PMID:22892286
Brain Oscillatory Activity during Spatial Navigation: Theta and Gamma Activity Link Medial Temporal and Parietal Regions
Boyer, Edmond
1 Brain Oscillatory Activity during Spatial Navigation: Theta and Gamma Activity Link Medial oscillatory correlates of spatial navigation were investigated using blind source separation (BSS-five participants were instructed to navigate to distinct landmark buildings in a previously learned virtual reality
Altered brain response to reward and punishment in adolescents with Anorexia Nervosa
Bischoff-Grethe, Amanda; McCurdy, Danyale; Grenesko-Stevens, Emily; (Zoe) Irvine, Laura E.; Wagner, Angela; Yau, Wai-Ying Wendy; Fennema-Notestine, Christine; Wierenga, Christina E.; Fudge, Julie L.; Delgado, Mauricio R.; Kaye, Walter H.
Adults recovered from anorexia nervosa (AN) have altered reward modulation within striatal limbic regions associated with the emotional significance of stimuli, and executive regions concerned with planning and consequences. We hypothesized that adolescents with AN would show similar disturbed reward modulation within the striatum and the anterior cingulate cortex, a region connected to the striatum and involved in reward-guided action selection. Using functional magnetic resonance imaging, twenty-two adolescent females (10 restricting-type AN, 12 healthy volunteers) performed a monetary guessing task. Time series data associated with monetary wins and losses within striatal and cingulate regions of interest were subjected to a linear mixed effects analysis. All participants responded more strongly to wins versus losses in limbic and anterior executive striatal territories. However, AN participants exhibited an exaggerated response to losses compared to wins in posterior executive and sensorimotor striatal regions, suggesting altered function in circuitry responsible for coding the affective context of stimuli and action selection based upon these valuations. As AN individuals are particularly sensitive to criticism, failure, and making mistakes, these findings may reflect the neural processes responsible for a bias in those with AN to exaggerate negative consequences. PMID:24148909
Classification of Types of Stuttering Symptoms Based on Brain Activity
Jiang, Jing; Lu, Chunming; Peng, Danling; Zhu, Chaozhe; Howell, Peter
Among the non-fluencies seen in speech, some are more typical (MT) of stuttering speakers, whereas others are less typical (LT) and are common to both stuttering and fluent speakers. No neuroimaging work has evaluated the neural basis for grouping these symptom types. Another long-debated issue is which type (LT, MT) whole-word repetitions (WWR) should be placed in. In this study, a sentence completion task was performed by twenty stuttering patients who were scanned using an event-related design. This task elicited stuttering in these patients. Each stuttered trial from each patient was sorted into the MT or LT types with WWR put aside. Pattern classification was employed to train a patient-specific single trial model to automatically classify each trial as MT or LT using the corresponding fMRI data. This model was then validated by using test data that were independent of the training data. In a subsequent analysis, the classification model, just established, was used to determine which type the WWR should be placed in. The results showed that the LT and the MT could be separated with high accuracy based on their brain activity. The brain regions that made most contribution to the separation of the types were: the left inferior frontal cortex and bilateral precuneus, both of which showed higher activity in the MT than in the LT; and the left putamen and right cerebellum which showed the opposite activity pattern. The results also showed that the brain activity for WWR was more similar to that of the LT and fluent speech than to that of the MT. These findings provide a neurological basis for separating the MT and the LT types, and support the widely-used MT/LT symptom grouping scheme. In addition, WWR play a similar role as the LT, and thus should be placed in the LT type. PMID:22761887
Brain Activity Associated with Emoticons: An fMRI Study
NASA Astrophysics Data System (ADS)
Yuasa, Masahide; Saito, Keiichi; Mukawa, Naoki
In this paper, we describe that brain activities associated with emoticons by using fMRI. In communication over a computer network, we use abstract faces such as computer graphics (CG) avatars and emoticons. These faces convey users' emotions and enrich their communications. However, the manner in which these faces influence the mental process is as yet unknown. The human brain may perceive the abstract face in an entirely different manner, depending on its level of reality. We conducted an experiment using fMRI in order to investigate the effects of emoticons. The results show that right inferior frontal gyrus, which associated with nonverbal communication, is activated by emoticons. Since the emoticons were created to reflect the real human facial expressions as accurately as possible, we believed that they would activate the right fusiform gyrus. However, this region was not found to be activated during the experiment. This finding is useful in understanding how abstract faces affect our behaviors and decision-making in communication over a computer network.
Altered Activity and Expression of Cytosolic Peptidases in Colorectal Cancer
Perez, Itxaro; Blanco, Lorena; Sanz, Begońa; Errarte, Peio; Ariz, Usue; Beitia, Maider; Fernández, Ainhoa; Loizate, Alberto; Candenas, M Luz; Pinto, Francisco M; Gil, Javier; López, José I.; Larrinaga, Gorka
Background and Objective: The role of peptidases in carcinogenic processes and their potential usefulness as tumor markers in colorectal cancer (CRC) have been classically attributed to cell-surface enzymes. The objective of the present study was to analyze the activity and mRNA expression of three cytosolic peptidases in the CRC and to correlate the obtained results with classic histopathological parameters for tumor prognosis and survival. Methods: The activity and mRNA levels of puromycin-sensitive aminopeptidase (PSA), aminopeptidase B (APB) and pyroglutamyl-peptidase I (PGI) were measured by fluorimetric and quantitative RT-PCR methods in colorectal mucosa and tumor tissues and plasma samples from CRC patients (n=81). Results: 1) PSA and APB activity was higher in adenomas and carcinomas than in the uninvolved mucosa. 2) mRNA levels of PSA and PGI was lower in tumors. 3) PGI activity in CRC tissue correlated negatively with histological grade, tumor size and 5-year overall suvival of CRC patients. 4) Higher plasmatic APB activity was independently associated with better 5-year overall survival. Conclusions: Data suggest that cytosolic peptidases may be involved in colorectal carcinogenesis and point to the determination of this enzymes as a valuable method in the determination of CRC prognosis.
Human sexual behavior related to pathology and activity of the brain.
Komisaruk, Barry R; Rodriguez Del Cerro, Maria Cruz
Reviewed in this chapter are: (1) correlations among human sexual behavior, brain pathology, and brain activity, including caveats regarding the interpretation of "cause and effect" among these factors, and the degree to which "hypersexuality" and reported changes in sexual orientation correlated with brain pathology are uniquely sexual or are attributable to a generalized disinhibition of brain function; (2) the effects, in some cases inhibitory, in others facilitatory, on sexual behavior and motivation, of stroke, epileptic seizures, traumatic brain injury, and brain surgery; and (3) insights into sexual motivation and behavior recently gained from functional brain imaging research and its interpretive limitations. We conclude from the reviewed research that the neural orchestra underlying the symphony of human sexuality comprises, rather than brain "centers," multiple integrated brain systems, and that there are more questions than answers in our understanding of the control of human sexual behavior by the brain - a level of understanding that is still in embryonic form. PMID:26003240
Catecholamine Contents of Different Region of Adult Rat Brain Are Altered Following Short and Long-term Exposures to Pb+2
Moshtaghie, Minoo; Malekpouri, Pedram; Saeed-zadeh, Mohammad; Messripour, Manuchehr; Moshtaghie, Ali Asghar
Catecholamine is a group of neurotransmitters that is believed to be responsible for the normal function of animal brain. Physiological and behavioral changes of human body have been reported due to the damage of the brain function following lead exposure. Due to the assumption of lead disposal in brain tissue with two year for its half-life, which results in alteration of brain function, we investigated the ability of lead to change the brain catecholamines during short and long-term studies. Rats were exposed daily with varying amounts of lead and catecholamine contents of cerebellum, mid-brain and brain cortex were determined. Acute peritoneal administration of single dose of lead as lead acetate (260 ?mol/Kg) after 2 h reduced (p < 0.05) the catecholamine levels of cerebellum, mid-brain and cortex part by 34.9%, 35.44% and 23.8%, respectively. The extension of experiment time to 5 h, significant (p < 0.05) reductions in catecholamine levels of mentioned regions of brain by 32.35%, 12.35% and 19.3% were seen respectively. Daily intraperitoneal administration of 10 ?mol/Kg lead for 30 and 60 days reduced catecholamines levels of cerebellum (22.22% and 30.44%), midbrain (12.48% and 26.27%) and brain cortex (11.58% and 26.7%) respectively. It might be concluded that brain dysfunction in lead intoxicated rat occurred through the reduction in the catecholamine levels of different parts of brain. Lead might be therefore considered as a probable factor in causing neurological disease in lead exposed man. PMID:24250622
Binge-like eating attenuates nisoxetine feeding suppression, stress activation, and brain norepinephrine activity.
Bello, Nicholas T; Yeh, Chung-Yang; Verpeut, Jessica L; Walters, Amy L
Stress is often associated with binge eating. A critical component of the control of stress is the central norepinephrine system. We investigated how dietary-induced binge eating alters central norepinephrine and related behaviors. Young male Sprague Dawley rats received calorie deprivation (24 h) and /or intermittent sweetened fat (vegetable shortening with sucrose; 30 min) twice a week for 10 weeks. The groups were Restrict Binge (calorie deprivation/sweetened fat), Binge (sweetened fat), Restrict (calorie deprivation), and Naive (no calorie deprivation/no sweetened fat). Dietary-induced binge eating was demonstrated by Restrict Binge and Binge, which showed an escalation in 30-min intake over time. Feeding suppression following nisoxetine (3 mg/kg; IP), a selective norepinephrine reuptake inhibitor, was not evident in Restrict Binge (Restrict Binge: 107±13, Binge: 52±9, Restrict: 80±8, Naive: 59±13% of saline injection at 1 h). In subsequent experiments with Restrict Binge and Naive, Restrict Binge had reduced corticosterone (Restrict Binge: 266±25; Naive: 494±36 ng/ml) and less feeding suppression (Restrict Binge: 81±12, Naive: 50±11% of non-restraint intake at 30 min) following restraint stress (1 h). Dietary-induced binge eating in Restrict Binge was not altered by a dorsal noradrenergic bundle lesion caused by N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), but frontal cortex norepinephrine was positively correlated with the average 30-min intake post-lesion (0.69; p<0.01). In a separate set of animals, single-unit in vivo electrophysiological recording of locus coeruleus-norepinephrine neural activity demonstrated reduced sensory-evoked response as a consequence of the Restrict Binge schedule (Restrict Binge: 8.1±0.67, Naive: 11.9±1.09 Hz). These results, which suggest that a consequence of dietary-induced binge eating is to attenuate the responsiveness of the brain norepinephrine system, will further our understanding of how highly palatable foods dampen the stress neuraxis. PMID:24695494
Methyl parathion activation by a partially purified rat brain fraction.
de Lima, J S; Bastos Neto, J da D; Bastos, V L; da Cunha, J C; Moraes, F F; Ferreira, M de F; Moreira, J da D; Faria, M V
Organophosphorus pesticides are one of the most commonly used insecticide classes. They act through a potent inhibition of acetylcholinesterase (AChE). Many of them must undergo transformation into the corresponding oxon analogs to inhibit AChE. This study showed that a brain tissue subfraction transformed methyl parathion (O,O-dimethyl O-p-nitrophenyl phosphorothioate) in vitro. Methyl parathion activation was assayed by solvent extraction of the products followed by HPLC and GC-MS analyses and, indirectly, by the inhibition of AChE present in the incubation mixture. The lack of impairment of AChE after 2 h of incubation of the brain subfraction with methyl parathion and, alternatively, with NADPH, CO, SKF 525-A, piperonyl butoxide or nitrogen indicated that this brain subfraction transformed methyl parathion without the involvement of a mixed-function oxidative pathway. The results from HPLC analysis did not show a peak corresponding to methyl paraoxon (O,O-dimethyl O-p-nitrophenylphosphate), but showed the production of an unidentified peak which eluted nearby standard methyl parathion (retention times of 10.65 and 8.86 min, respectively). GC-MS analysis suggested that the unidentified product could be a methyl parathion isomer. PMID:8701445
Altered Error-Related Activity in Patients with Schizophrenia
ERIC Educational Resources Information Center
Koch, Kathrin; Wagner, Gerd; Schultz, Christoph; Schachtzabel, Claudia; Nenadic, Igor; Axer, Martina; Reichenbach, Jurgen R.; Sauer, Heinrich; Schlosser, Ralf G. M.
Deficits in working memory (WM) and executive cognitive control are core features of schizophrenia. However, findings regarding functional activation strengths are heterogeneous, partly due to differences in task demands and behavioral performance. Previous investigators proposed integrating these heterogeneous findings into a comprehensive model…
Acute neuroactive drug exposures alter locomotor activity in larval zebrafish
In an effort to develop a rapid in vivo screen for EPA's prioritization of toxic chemicals, we are characterizing the locomotor activity of zebrafish (Danio rerio) larvae after exposure to prototypic drugs that act on the central nervous system. MPTP (1-methyl-4phenyl- 1 ,2,3,6-...
Acute Neuroactive Drug Exposures alter Locomotor Activity in Larval Zebrafish
As part of the development of a rapid in vivo screen for prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae by assessing the acute effects of prototypic drugs that act on the central nervous system. Initially,...
Alterations in Skin and Stratified Epithelia by Constitutively Activated PPARa
Omiecinski, Curtis
resulted in postnatal lethality within 2 days after birth. A thin epidermis, few hair follicles the tetracycline Tet-off regulatory system to target constitutively activated PPARa to the epidermis and other-responsive elements, in the promotors of target genes (Berger and Moller, 2002). Consequently, the PPARs regulate
Altered glycaemia differentially modulates efflux transporter expression and activity in hCMEC/D3 cell line.
Sajja, Ravi K; Cucullo, Luca
The unique phenotype of blood-brain barrier (BBB) endothelium is partly maintained by abundant expression of ATP-binding cassette superfamily of efflux transporters that strictly restrict the CNS access to toxic substances including xenobiotics in circulation. Previously, we have shown that diabetes-related altered glycemic conditions differentially affect and compromise BBB integrity. However, the impact of diabetes on BBB efflux transporters is less understood. In this study, we examined the effects of single or repeated episodes of hypo-and hyperglycemia on major BBB efflux transporters expression/function in human cerebromicrovascular endothelial cell line (hCMEC/D3). Cells were exposed to normal (5.5mM), hypo (2.2mM) or hyper (25 or 35mM)-glycemic media containing d-glucose for 12h (acute) or two 3h episodes/day of hypo- or hyperglycemia with an intercalated 2h normalglycemic exposure for 3 days ("glycemic variability", see Methods). Acute hypoglycemic exposure (12h) up-regulated BBB endothelial mRNA and protein expression of P-glycoprotein, BCRP and other multidrug resistance associated proteins (MRP1 and 4) paralleled by an increase in transporter-specific efflux activity (?2-fold vs. control). Although, 12h hyperglycemia did not affect the efflux transporter expression (except for MRP4), a significant increase in BCRP activity was observed. By contrast, DNA microarray data revealed that repeated hyperglycemic episodes (but not hypoglycemia) significantly up-regulate P-glycoprotein expression and activity. Thus, this study suggests a differential impact of altered glycemic conditions on major BBB drug efflux transporters expression/function, sensitive to the length of exposure (acute vs. repeated), with an implication for altered CNS drug disposition in diabetic population. PMID:25982326
Neurotrophin Receptor Activation and Expression in Human Postmortem Brain: Effect of Suicide
Dwivedi, Yogesh; Rizavi, Hooriyah S.; Zhang, Hui; Mondal, Amal C.; Roberts, Rosalinda C.; Conley, Robert R.; Pandey, Ghanshyam N.
Background The physiological functions of neurotrophins occur through binding to two different receptors: pan75 neurotrophin receptor (p75NTR) and a family of tropomysin receptor kinases (Trks A, B, and C). Recently, we reported that expression of neurotrophins and TrkB were reduced in brains of suicide subjects. Present study examines whether expression and activation of Trk receptors and expression of p75NTR are altered in brain of these subjects. Methods Expression levels of TrkA, B, C, and of p75NTR were measured by quantitative RT-PCR and Western blot in prefrontal cortex (PFC) and hippocampus of suicide and normal control subjects. The activation of Trks was determined by immunoprecipitation followed by Western blotting using phosphotyrosine antibody. Results In hippocampus, lower mRNA levels of TrkA and TrkC were observed in suicide subjects. In the PFC, the mRNA level of TrkA was decreased, without any change in TrkC. On the other hand, the mRNA level of p75NTR was increased in both PFC and hippocampus. Immunolabeling studies showed similar results as observed for the mRNAs. In addition, phosphorylation of all Trks was decreased in hippocampus, but in PFC, decreased phosphorylation was noted only for TrkA and B. Increased expression ratios of p75NTR to Trks were also observed in PFC and hippocampus of suicide subjects. Conclusions Our results suggest not only reduced functioning of Trks in brains of suicide subjects but that increased ratios of p75NTR to Trks indicate possible activation of pathways that are apoptotic in nature. These findings may be crucial in the pathophysiology of suicide. PMID:18930453
Alterations of human electroencephalographic activity caused by multiple extremely low frequency magnetic field exposures
Dean Cvetkovic; Irena Cosic
In the past, many studies have claimed that extremely low frequency (ELF) magnetic field (MF) exposures could alter the human\\u000a electroencephalographic (EEG) activity. This study aims at extending our ELF pilot study to investigate whether MF exposures\\u000a at ELF in series from 50, 16.66, 13, 10, 8.33 to 4 Hz could alter relative power within the corresponding EEG bands. 33 human
Calcium imaging of infrared-stimulated activity in rodent brain
Cayce, Jonathan Matthew; Bouchard, Matthew B.; Chernov, Mykyta M.; Chen, Brenda R.; Grosberg, Lauren E.; Jansen, E. Duco; Hillman, Elizabeth M. C.; Mahadevan-Jansen, Anita
Summary Infrared neural stimulation (INS) is a promising neurostimulation technique that can activate neural tissue with high spatial precision and without the need for exogenous agents. However, little is understood about how infrared light interacts with neural tissue on a cellular level, particularly within the living brain. In this study, we use calcium sensitive dye imaging on macroscopic and microscopic scales to explore the spatiotemporal effects of INS on cortical calcium dynamics. The INS-evoked calcium signal that was observed exhibited a fast and slow component suggesting activation of multiple cellular mechanisms. The slow component of the evoked signal exhibited wave-like properties suggesting network activation, and was verified to originate from astrocytes through pharmacology and 2-photon imaging. We also provide evidence that the fast calcium signal may have been evoked through modulation of glutamate transients. This study demonstrates that pulsed infrared light can induce intracellular calcium modulations in both astrocytes and neurons, providing new insights into the mechanisms of action of INS in the brain. PMID:24674600
Calcium imaging of infrared-stimulated activity in rodent brain.
Cayce, Jonathan Matthew; Bouchard, Matthew B; Chernov, Mykyta M; Chen, Brenda R; Grosberg, Lauren E; Jansen, E Duco; Hillman, Elizabeth M C; Mahadevan-Jansen, Anita
Infrared neural stimulation (INS) is a promising neurostimulation technique that can activate neural tissue with high spatial precision and without the need for exogenous agents. However, little is understood about how infrared light interacts with neural tissue on a cellular level, particularly within the living brain. In this study, we use calcium sensitive dye imaging on macroscopic and microscopic scales to explore the spatiotemporal effects of INS on cortical calcium dynamics. The INS-evoked calcium signal that was observed exhibited a fast and slow component suggesting activation of multiple cellular mechanisms. The slow component of the evoked signal exhibited wave-like properties suggesting network activation, and was verified to originate from astrocytes through pharmacology and 2-photon imaging. We also provide evidence that the fast calcium signal may have been evoked through modulation of glutamate transients. This study demonstrates that pulsed infrared light can induce intracellular calcium modulations in both astrocytes and neurons, providing new insights into the mechanisms of action of INS in the brain. PMID:24674600
Biometrics from brain electrical activity: a machine learning approach.
Palaniappan, Ramaswamy; Mandic, Danilo P
The potential of brain electrical activity generated as a response to a visual stimulus is examined in the context of the identification of individuals. Specifically, a framework for the Visual Evoked Potential (VEP)-based biometrics is established, whereby energy features of the gamma band within VEP signals were of particular interest. A rigorous analysis is conducted which unifies and extends results from our previous studies, in particular, with respect to 1) increased bandwidth, 2) spatial averaging, 3) more robust power spectrum features, and 4) improved classification accuracy. Simulation results on a large group of subject support the analysis. PMID:17299228
Nonlinear changes in brain electrical activity due to cell phone radiation.
Marino, Andrew A; Nilsen, Erik; Frilot, Clifton
We studied the effect of an electromagnetic field from a cellular telephone on brain electrical activity, using a novel analytical method based on a nonlinear model. The electroencephalogram (EEG) from rabbits was embedded in phase space and local recurrence plots were calculated and quantified using recurrence quantitation analysis to permit statistical comparisons between filtered segments of exposed and control epochs from individual rabbits. When the rabbits were exposed to the radiation from a standard cellular telephone (800 MHz band, 600 mW maximum radiated power) under conditions that simulated normal human use, the EEG was significantly affected in nine of ten animals studied. The effect occurred beginning about 100 ms after initiation of application of the field and lasted approximately 300 ms. In each case, the fields increased the randomness in the EEG. A control procedure ruled out the possibility that the observations were a product of the method of analysis. No differences were found between exposed and control epochs in any animal when the experiment was repeated after the rabbits had been sacrificed, indicating that absorption of radiation by the EEG electrodes could not account for the observed effect. No effect was seen when deposition of energy in the brain was minimized by repositioning the radiating antenna from the head to the chest, showing that the type of tissue that absorbed the energy determined the observed changes in the EEG. We conclude that, in normal use, the fields from a standard cellular telephone can alter brain function as a consequence of absorption of energy by the brain. PMID:12820291
Alteration of the Specificity of Malate Dehydrogenase by Chemical Modulation of an Active Site Arginine*
Viola, Ronald
Alteration of the Specificity of Malate Dehydrogenase by Chemical Modulation of an Active Site the Department of Chemistry, University of Toledo, Toledo, Ohio 43606 Malate dehydrogenase from Escherichia coli of a range of functional groups at the active site of malate dehydrogenase. The introduction of a positively
Lack of serotonin reuptake during brain development alters rostral raphe-prefrontal network formation
Witteveen, Josefine S.; Middelman, Anthonieke; van Hulten, Josephus A.; Martens, Gerard J. M.; Homberg, Judith R.; Kolk, Sharon M.
Besides its "classical" neurotransmitter function, serotonin (5-HT) has been found to also act as a neurodevelopmental signal. During development, the 5-HT projection system, besides an external placental source, represents one of the earliest neurotransmitter systems to innervate the brain. One of the targets of the 5-HT projection system, originating in the brainstem raphe nuclei, is the medial prefrontal cortex (mPFC), an area involved in higher cognitive functions and important in the etiology of many neurodevelopmental disorders. Little is known, however, about the exact role of 5-HT and its signaling molecules in the formation of the raphe-prefrontal network. Using explant essays, we here studied the role of the 5-HT transporter (5-HTT), an important modulator of the 5-HT signal, in rostral raphe-prefrontal network formation. We found that the chemotrophic nature of the interaction between the origin (rostral raphe cluster) and a target (mPFC) of the 5-HT projection system was affected in rats lacking the 5-HTT (5-HTT?/?). While 5-HTT deficiency did not affect the dorsal raphe 5-HT-positive outgrowing neurites, the median raphe 5-HT neurites switched from a strong repulsive to an attractive interaction when co-cultured with the mPFC. Furthermore, the fasciculation of the mPFC outgrowing neurites was dependent on the amount of 5-HTT. In the mPFC of 5-HTT?/? pups, we observed clear differences in 5-HT innervation and the identity of a class of projection neurons of the mPFC. In the absence of the 5-HTT, the 5-HT innervation in all subareas of the early postnatal mPFC increased dramatically and the number of Satb2-positive callosal projection neurons was decreased. Together, these results suggest a 5-HTT dependency during early development of these brain areas and in the formation of the raphe-prefrontal network. The tremendous complexity of the 5-HT projection system and its role in several neurodevelopmental disorders highlights the need for further research in this largely unexplored area. PMID:24109430
Morphological and biochemical alterations activated by antitumor clerodane diterpenes.
Ferreira, Paulo Michel Pinheiro; Milităo, Gardenia Carmen Gadelha; Lima, Daisy Jereissati Barbosa; Costa, Nagilla Daniela de Jesus; Machado, Kátia da Conceiçăo; Santos, André Gonzaga Dos; Cavalheiro, Alberto José; Bolzani, Vanderlan da Silva; Silva, Dulce Helena Siqueira; Pessoa, Cláudia
Casearia sylvestris Swartz (Salicaceae) is a plant commonly widespread in the Americas. It has oxygenated tricyclic bioactive clerodane diterpenes with antimicrobial, antiulcer, larvicidal, chemopreventive, anti-inflammatory, antioxidant and antiproliferative properties. Due to this requirement for the developing of new anticancer drugs, it was initially evaluated the cytotoxic activity of a fraction with Casearins (FC) and its clerodane diterpenes Casearin B (Cas B), D (Cas D), X (Cas X) and Caseargrewiin F (Cas F) isolated from C.sylvestris leaves against 7 tumor cell lines, Sarcoma 180 cells (S180) and on normal peripheral blood mononuclear cells (PBMC). All substances tested showed cytotoxic potential. Cas F and X were the most active compounds. Cell death analyzes with Cas F (0.5 and 1?M) and Cas X (0.7 and 1.5?M) using the HL-60 leukemia line as experimental model showed DNA synthesis and membrane integrity reduction, DNA fragmentation and mitochondrial depolarization, specially after 24h exposure, cell cycle arrest in G0/G1 phase caused by Cas X, activation of the initiator -8/-9 and effector -3/-7 caspases and phosphatidylserine externalization, all biochemical features of apoptosis corroborated by chromatinic condensation, karyorrhexis, cytoplasmic vacuolation and rarefaction and cellular shrinkage, morphological findings specially observed after 12 and 24h of incubation. Therefore, Cas X and F were the most functional molecules with more pronounced lethal and discriminating effects on tumor cells and antiproliferative action predominantly mediated by apoptosis, highlighting clerodane dipertenes as promising lead antineoplastic compounds. PMID:25452174
Metabolic alterations in corpus callosum may compromise brain functional connectivity in MTBI patients: an 1H-MRS study
Johnson, Brian; Zhang, Kai; Gay, Michael; Neuberger, Thomas; Horovitz, Silvina; Hallett, Mark; Sebastianelli, Wayne; Slobounov, Semyon
After clinical resolution of signs and symptoms of mild traumatic brain injury (MTBI) it is still not clear if there are residual abnormalities of structural or functional brain networks. We have previously documented disrupted interhemispheric functional connectivity in "asymptomatic" concussed individuals during the sub-acute phase of injury. Testing of 15 normal volunteers (NV) and 15 subacute MTBI subjects was performed within 24 hours of clinical symptoms resolution and medical clearance for the first stage of aerobic activity. In this MRS study we report (a) both in the genu and splenium of the corpus callosum NAA/Cho and NAA/Cr ratios were significantly (p<0.05) lower in MTBI subjects shortly after the injury compared to NVs, and (b) the metabolic ratio NAA/Cho in the splenium significantly correlated with the magnitude of inter-hippocampal functional connectivity in normal volunteers, but not in MTBI. This novel finding supports our hypothesis that the functional disruption of interhemispheric brain networks in MTBI subjects results from compromised metabolic integrity of the corpus callosum and that this persists despite apparent clinical return to baseline. PMID:22108503
Altered 8-oxoguanine glycosylase in mild cognitive impairment and late-stage Alzheimer's disease brain
Shao, Changxing; Xiong, Shuling; Li, Guo-Min; Gu, Liya; Mao, Guogen; Markesbery, William R.; Lovell, Mark A.
Eight-hydroxy-2?-deoxyguanosine (8-OHdG) is increased in the brain in late-stage Alzheimer's disease (LAD) and mild cognitive impairment (MCI). To determine if decreased base-excision repair contributes to these elevations, we measured oxoguanine glycosylase 1 (OGG1) protein and incision activities in nuclear and mitochondrial fractions from frontal (FL), temporal (TL), and parietal (PL) lobes from 8 MCI and 7 LAD patients, and 6 age-matched normal control (NC) subjects. OGG1 activity was significantly (P<0.05) decreased in nuclear specimens of FL, TL, and PL in MCI and LAD and in mitochondria from LAD FL and TL and MCI TL. Nuclear OGG1 protein was significantly decreased in LAD FL and MCI and LAD PL. No differences in mitochondrial OGG1 protein levels were found. Overall, our results suggest that decreased OGG1 activity occurs early in the progression of AD, possibly mediated by 4-hydroxynonenal inactivation and may contribute to elevated 8-OHdG in the brain in MCI and LAD. PMID:18598755
Inaudible high-frequency sounds affect brain activity: hypersonic effect.
Oohashi, T; Nishina, E; Honda, M; Yonekura, Y; Fuwamoto, Y; Kawai, N; Maekawa, T; Nakamura, S; Fukuyama, H; Shibasaki, H
Although it is generally accepted that humans cannot perceive sounds in the frequency range above 20 kHz, the question of whether the existence of such "inaudible" high-frequency components may affect the acoustic perception of audible sounds remains unanswered. In this study, we used noninvasive physiological measurements of brain responses to provide evidence that sounds containing high-frequency components (HFCs) above the audible range significantly affect the brain activity of listeners. We used the gamelan music of Bali, which is extremely rich in HFCs with a nonstationary structure, as a natural sound source, dividing it into two components: an audible low-frequency component (LFC) below 22 kHz and an HFC above 22 kHz. Brain electrical activity and regional cerebral blood flow (rCBF) were measured as markers of neuronal activity while subjects were exposed to sounds with various combinations of LFCs and HFCs. None of the subjects recognized the HFC as sound when it was presented alone. Nevertheless, the power spectra of the alpha frequency range of the spontaneous electroencephalogram (alpha-EEG) recorded from the occipital region increased with statistical significance when the subjects were exposed to sound containing both an HFC and an LFC, compared with an otherwise identical sound from which the HFC was removed (i.e., LFC alone). In contrast, compared with the baseline, no enhancement of alpha-EEG was evident when either an HFC or an LFC was presented separately. Positron emission tomography measurements revealed that, when an HFC and an LFC were presented together, the rCBF in the brain stem and the left thalamus increased significantly compared with a sound lacking the HFC above 22 kHz but that was otherwise identical. Simultaneous EEG measurements showed that the power of occipital alpha-EEGs correlated significantly with the rCBF in the left thalamus. Psychological evaluation indicated that the subjects felt the sound containing an HFC to be more pleasant than the same sound lacking an HFC. These results suggest the existence of a previously unrecognized response to complex sound containing particular types of high frequencies above the audible range. We term this phenomenon the "hypersonic effect." PMID:10848570
Imaging of brain tumor proliferative activity with iodine-131-iododeoxyuridine
Tjuvajev, J.G.; Macapinlac, H.A.; Daghighian, F. [Cotzias Neuro-Oncology Lab., New York, NY (United States)] [and others
Iodine-131-iododeoxyuridine (IUdR) uptake and retention was imaged with SPECT at 2 and 24 hr after administering a 10-mCi dose to six patients with primary brain tumors. The SPECT images were directly compared to gadolinium contrast-enhanced MR images as well as to ({sup 18}F) fluorodeoxyglucose (FDG) PET scans and {sup 201}Tl SPECT scans. Localized uptake and retention of IUdR-derived radioactivity was observed in five of six patients. The plasma half-life of ({sup 131}I) IUdR was short (1.5 min) in comparison to the half-life of total plasma radioactivity (6.4 hr). The pattern of ({sup 131}I)IUdR-derived radioactivity was markedly different in the 2-hr compared to 24-hr images. Radioactivity was localized along the periphery of the tumor and extended beyond the margin of tumor identified by contrast enhancement on MRI. The estimated levels of tumor radioactivity at 24 hr, based on semiquantitative phantom studies, ranged between <0.1 and 0.2 {mu}Ci/cc (<0.001% and 0.002% dose/cc); brain levels were not measurable. Iodine-131-IUdR SPECT imaging of brain tumor proliferation has low (marginal) sensitivity due to low count rates and can detect only the most active regions of tumor growth. Imaging at 24 hr represents a washout strategy to reduce {sup 131}I-labeled metabolites contributing to background activity in the tumors, and is more likely to show the pattern of ({sup 131}I)IUdR-DNA incorporation and thereby increase image specificity. Iodine-123-IUdR SPECT imaging at 12 hr and the use of ({sup 124}I)IUdR and PET will improve count acquisitions and image quality. 74 refs., 6 figs., 2 tabs.
Abnormal Baseline Brain Activity in Patients with Pulsatile Tinnitus: A Resting-State fMRI Study
Han, Lv; Zhaohui, Liu; Fei, Yan; Ting, Li; Pengfei, Zhao; Wang, Du; Cheng, Dong; Pengde, Guo; Xiaoyi, Han; Xiao, Wang; Rui, Li; Zhenchang, Wang
Numerous investigations studying the brain functional activity of the tinnitus patients have indicated that neurological changes are important findings of this kind of disease. However, the pulsatile tinnitus (PT) patients were excluded in previous studies because of the totally different mechanisms of the two subtype tinnitus. The aim of this study is to investigate whether altered baseline brain activity presents in patients with PT using resting-state functional magnetic resonance imaging (rs-fMRI) technique. The present study used unilateral PT patients (n = 42) and age-, sex-, and education-matched normal control subjects (n = 42) to investigate the changes in structural and amplitude of low-frequency (ALFF) of the brain. Also, we analyzed the relationships between these changes with clinical data of the PT patients. Compared with normal controls, PT patients did not show any structural changes. PT patients showed significant increased ALFF in the bilateral precuneus, and bilateral inferior frontal gyrus (IFG) and decreased ALFF in multiple occipital areas. Moreover, the increased THI score and PT duration was correlated with increased ALFF in precuneus and bilateral IFG. The abnormalities of spontaneous brain activity reflected by ALFF measurements in the absence of structural changes may provide insights into the neural reorganization in PT patients. PMID:24872895
The situated HKB model: how sensorimotor spatial coupling can alter oscillatory brain dynamics.
Aguilera, Miguel; Bedia, Manuel G; Santos, Bruno A; Barandiaran, Xabier E
Despite the increase of both dynamic and embodied/situated approaches in cognitive science, there is still little research on how coordination dynamics under a closed sensorimotor loop might induce qualitatively different patterns of neural oscillations compared to those found in isolated systems. We take as a departure point the Haken-Kelso-Bunz (HKB) model, a generic model for dynamic coordination between two oscillatory components, which has proven useful for a vast range of applications in cognitive science and whose dynamical properties are well understood. In order to explore the properties of this model under closed sensorimotor conditions we present what we call the situated HKB model: a robotic model that performs a gradient climbing task and whose "brain" is modeled by the HKB equation. We solve the differential equations that define the agent-environment coupling for increasing values of the agent's sensitivity (sensor gain), finding different behavioral strategies. These results are compared with two different models: a decoupled HKB with no sensory input and a passively-coupled HKB that is also decoupled but receives a structured input generated by a situated agent. We can precisely quantify and qualitatively describe how the properties of the system, when studied in coupled conditions, radically change in a manner that cannot be deduced from the decoupled HKB models alone. We also present the notion of neurodynamic signature as the dynamic pattern that correlates with a specific behavior and we show how only a situated agent can display this signature compared to an agent that simply receives the exact same sensory input. To our knowledge, this is the first analytical solution of the HKB equation in a sensorimotor loop and qualitative and quantitative analytic comparison of spatially coupled vs. decoupled oscillatory controllers. Finally, we discuss the limitations and possible generalization of our model to contemporary neuroscience and philosophy of mind. PMID:23986692
The situated HKB model: how sensorimotor spatial coupling can alter oscillatory brain dynamics
Aguilera, Miguel; Bedia, Manuel G.; Santos, Bruno A.; Barandiaran, Xabier E.
Despite the increase of both dynamic and embodied/situated approaches in cognitive science, there is still little research on how coordination dynamics under a closed sensorimotor loop might induce qualitatively different patterns of neural oscillations compared to those found in isolated systems. We take as a departure point the Haken-Kelso-Bunz (HKB) model, a generic model for dynamic coordination between two oscillatory components, which has proven useful for a vast range of applications in cognitive science and whose dynamical properties are well understood. In order to explore the properties of this model under closed sensorimotor conditions we present what we call the situated HKB model: a robotic model that performs a gradient climbing task and whose "brain" is modeled by the HKB equation. We solve the differential equations that define the agent-environment coupling for increasing values of the agent's sensitivity (sensor gain), finding different behavioral strategies. These results are compared with two different models: a decoupled HKB with no sensory input and a passively-coupled HKB that is also decoupled but receives a structured input generated by a situated agent. We can precisely quantify and qualitatively describe how the properties of the system, when studied in coupled conditions, radically change in a manner that cannot be deduced from the decoupled HKB models alone. We also present the notion of neurodynamic signature as the dynamic pattern that correlates with a specific behavior and we show how only a situated agent can display this signature compared to an agent that simply receives the exact same sensory input. To our knowledge, this is the first analytical solution of the HKB equation in a sensorimotor loop and qualitative and quantitative analytic comparison of spatially coupled vs. decoupled oscillatory controllers. Finally, we discuss the limitations and possible generalization of our model to contemporary neuroscience and philosophy of mind. PMID:23986692
Longitudinal Brain White Matter Alterations in Minimal Hepatic Encephalopathy before and after Liver Transplantation
Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chao-Long; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Huang, Chu-Chung; Lin, Ching-Po; Cheng, Yu-Fan
Cerebral edema is the common pathogenic mechanism for cognitive impairment in minimal hepatic encephalopathy. Whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved after liver transplantation remains an open question. To characterize white matter integrity before and after liver transplantation in patients with minimal hepatic encephalopathy, multiple diffusivity indices acquired via diffusion tensor imaging was applied. Twenty-eight patients and thirty age- and sex-matched healthy volunteers were included. Multiple diffusivity indices were obtained from diffusion tensor images, including mean diffusivity, fractional anisotropy, axial diffusivity and radial diffusivity. The assessment was repeated 6–12 month after transplantation. Differences in white matter integrity between groups, as well as longitudinal changes, were evaluated using tract-based spatial statistical analysis. Correlation analyses were performed to identify first scan before transplantation and interval changes among the neuropsychiatric tests, clinical laboratory tests, and diffusion tensor imaging indices. After transplantation, decreased water diffusivity without fractional anisotropy change indicating reversible cerebral edema was found in the left anterior cingulate, claustrum, postcentral gyrus, and right corpus callosum. However, a progressive decrease in fractional anisotropy and an increase in radial diffusivity suggesting demyelination were noted in temporal lobe. Improved pre-transplantation albumin levels and interval changes were associated with better recoveries of diffusion tensor imaging indices. Improvements in interval diffusion tensor imaging indices in the right postcentral gyrus were correlated with visuospatial function score correction. In conclusion, longitudinal voxel-wise analysis of multiple diffusion tensor imaging indices demonstrated different white matter changes in minimal hepatic encephalopathy patients. Transplantation improved extracellular cerebral edema and the results of associated cognition tests. However, white matter demyelination may advance in temporal lobe. PMID:25166619
Single housing during early adolescence causes time-, area- and peptide-specific alterations in endogenous opioids of rat brain
Granholm, L; Roman, E; Nylander, I
BACKGROUND AND PURPOSE A number of experimental procedures require single housing to assess individual behaviour and physiological responses to pharmacological treatments. The endogenous opioids are closely linked to social interaction, especially early in life, and disturbance in the social environment may affect opioid peptides and thereby confound experimental outcome. The aim of the present study was to examine time-dependent effects of single housing on opioid peptides in rats. EXPERIMENTAL APPROACH Early adolescent Sprague Dawley rats (post-natal day 22) were subjected to either prolonged (7 days) or short (30 min) single housing. Several brain regions were dissected and immunoreactive levels of Met-enkephalin-Arg6Phe7 (MEAP), dynorphin B and nociception/orphanin FQ, as well as serum corticosterone were measured using RIA. KEY RESULTS Prolonged single housing reduced immunoreactive MEAP in hypothalamus, cortical regions, amygdala, substantia nigra and periaqueductal grey. Short single housing resulted in an acute stress response as indicated by high levels of corticosterone, accompanied by elevated immunoreactive nociceptin/orphanin FQ in medial prefrontal cortex, nucleus accumbens and amygdala. Neither short nor prolonged single housing affected dynorphin B. CONCLUSIONS AND IMPLICATIONS Disruption in social environmental conditions of rats, through single housing during early adolescence, resulted in time-, area- and peptide-specific alterations in endogenous opioids in the brain. These results provide further evidence for an association between early life social environment and opioids. Furthermore, the results have implications for experimental design; in any pharmacological study involving opioid peptides, it is important to distinguish between effects induced by housing and treatment. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24821004
Motor cortical prediction of EMG: evidence that a kinetic brain-machine interface may be robust across altered movement dynamics
Cherian, A.; Krucoff, M. O.
During typical movements, signals related to both the kinematics and kinetics of movement are mutually correlated, and each is correlated to some extent with the discharge of neurons in the primary motor cortex (M1). However, it is well known, if not always appreciated, that causality cannot be inferred from correlations. Although these mutual correlations persist, their nature changes with changing postural or dynamical conditions. Under changing conditions, only signals directly controlled by M1 can be expected to maintain a stable relationship with its discharge. If one were to rely on noncausal correlations for a brain-machine interface, its generalization across conditions would likely suffer. We examined this effect, using multielectrode recordings in M1 as input to linear decoders of both end point kinematics (position and velocity) and proximal limb myoelectric signals (EMG) during reaching. We tested these decoders across tasks that altered either the posture of the limb or the end point forces encountered during movement. Within any given task, the accuracy of the kinematic predictions tended to be somewhat better than the EMG predictions. However, when we used the decoders developed under one task condition to predict the signals recorded under different postural or dynamical conditions, only the EMG decoders consistently generalized well. Our results support the view that M1 discharge is more closely related to kinetic variables like EMG than it is to limb kinematics. These results suggest that brain-machine interface applications using M1 to control kinetic variables may prove to be more successful than the more standard kinematic approach. PMID:21562185
Metabolic alterations induced in cultured skeletal muscle by stretch-relaxation activity
NASA Technical Reports Server (NTRS)
Hatfaludy, Sophia; Shansky, Janet; Vandenburgh, Herman H.
Muscle cells differentiated in vitro are repetitively stretched and relaxed in order to determine the presence of short- and long-term alterations occurring in glucose uptake and lactate efflux that are similar to the metabolic alterations occurring in stimulated organ-cultured muscle and in vivo skeletal muscle during the active state. It is observed that whereas mechanical stimulation increases these metabolic parameters within 4-6 h of starting activity, unstimulated basal rates in control cultures also increase during this period of time, and by 8 h, their rates have reached or exceeded the rates in continuously stimulated cells. Measurements of these parameters in media of different compositions show that activity-induced long-term alterations in the parameters occur independently of growth factors in serium and embryo extracts.
EEGSOLVER -BRAIN ACTIVITY AND GENETIC ALGORITHMS Paulo Aguiar Andr6 David Sandra Paulo Agostinho Rosa
Boetticher, Gary D.
an electroencephalogram (EEG), findingout where the spots of activity in the brain are. Our Brain is a mysterious machine Electroencephalogram Every moment our brain cells generate millions of nervous impulses (nerve action potentials. A record of such waves is named electroencephalogram (EEG). The human EEG was discovered by Berger (1929
Targeted training modifies oscillatory brain activity in schizophrenia patients
Popov, Tzvetan G.; Carolus, Almut; Schubring, David; Popova, Petia; Miller, Gregory A.; Rockstroh, Brigitte S.
Effects of both domain-specific and broader cognitive remediation protocols have been reported for neural activity and overt performance in schizophrenia (SZ). Progress is limited by insufficient knowledge of relevant neural mechanisms. Addressing neuronal signal resolution in the auditory system as a mechanism contributing to cognitive function and dysfunction in schizophrenia, the present study compared effects of two neuroplasticity-based training protocols targeting auditory–verbal or facial affect discrimination accuracy and a standard rehabilitation protocol on magnetoencephalographic (MEG) oscillatory brain activity in an auditory paired-click task. SZ were randomly assigned to either 20 daily 1-hour sessions over 4 weeks of auditory–verbal training (N = 19), similarly intense facial affect discrimination training (N = 19), or 4 weeks of treatment as usual (TAU, N = 19). Pre-training, the 57 SZ showed smaller click-induced posterior alpha power modulation than did 28 healthy comparison participants, replicating Popov et al. (2011b). Abnormally small alpha decrease 300–800 ms around S2 improved more after targeted auditory–verbal training than after facial affect training or TAU. The improvement in oscillatory brain dynamics with training correlated with improvement on a measure of verbal learning. Results replicate previously reported effects of neuroplasticity-based psychological training on oscillatory correlates of auditory stimulus differentiation, encoding, and updating and indicate specificity of cortical training effects.
Altered free radical metabolism in acute mountain sickness: implications for dynamic cerebral autoregulation and blood–brain barrier function
Bailey, D M; Evans, K A; James, P E; McEneny, J; Young, I S; Fall, L; Gutowski, M; Kewley, E; McCord, J M; Mřller, Kirsten; Ainslie, P N
We tested the hypothesis that dynamic cerebral autoregulation (CA) and blood–brain barrier (BBB) function would be compromised in acute mountain sickness (AMS) subsequent to a hypoxia-mediated alteration in systemic free radical metabolism. Eighteen male lowlanders were examined in normoxia (21% O2) and following 6 h passive exposure to hypoxia (12% O2). Blood flow velocity in the middle cerebral artery (MCAv) and mean arterial blood pressure (MAP) were measured for determination of CA following calculation of transfer function analysis and rate of regulation (RoR). Nine subjects developed clinical AMS (AMS+) and were more hypoxaemic relative to subjects without AMS (AMS–). A more marked increase in the venous concentration of the ascorbate radical (A•?), lipid hydroperoxides (LOOH) and increased susceptibility of low-density lipoprotein (LDL) to oxidation was observed during hypoxia in AMS+ (P < 0.05 versus AMS–). Despite a general decline in total nitric oxide (NO) in hypoxia (P < 0.05 versus normoxia), the normoxic baseline plasma and red blood cell (RBC) NO metabolite pool was lower in AMS+ with normalization observed during hypoxia (P < 0.05 versus AMS–). CA was selectively impaired in AMS+ as indicated both by an increase in the low-frequency (0.07–0.20Hz) transfer function gain and decrease in RoR (P < 0.05 versus AMS–). However, there was no evidence for cerebral hyper-perfusion, BBB disruption or neuronal–parenchymal damage as indicated by a lack of change in MCAv, S100? and neuron-specific enolase. In conclusion, these findings suggest that AMS is associated with altered redox homeostasis and disordered CA independent of barrier disruption. PMID:18936082
Brain Activity During Landmark and Line Bisection Tasks
Çiçek, Metehan; Deouell, Leon Y.; Knight, Robert T.
Neglect patients bisect lines far rightward of center whereas normal subjects typically bisect lines with a slight leftward bias supporting a right hemisphere bias for attention allocation. We used fMRI to assess the brain regions related to this function in normals, using two complementary tasks. In the Landmark task subjects were required to judge whether or not a presented line was bisected correctly. During the line bisection task, subjects moved a cursor and indicated when it reached the center of the line. The conjunction of BOLD activity for both tasks showed right lateralized intra-parietal sulcus and lateral peristriate cortex activity. The results provide evidence that predominantly right hemisphere lateralized processes are engaged in normal subjects during tasks that are failed in patients with unilateral neglect and highlight the importance of a right fronto-parietal network in attention allocation. PMID:19521543
Thomas W. Custer; Harry M. Ohlendorf
Inhibition of brain cholinesterase (ChE) activity in birds is often used to diagnose exposure or death from organophosphorus or carbamate pesticides. Brain ChE activity in the young of altricial species increases with age; however, this relationship has only been demonstrated in tile European starling (Sturnus vulgaris). Brain ChE activity of nestling great egrets (Casme- rodius albus) collected from a colony
Subchronic atrazine exposure changes defensive behaviour profile and disrupts brain acetylcholinesterase activity of zebrafish.
Schmidel, Ademir J; Assmann, Karla L; Werlang, Chariane C; Bertoncello, Kanandra T; Francescon, Francini; Rambo, Cassiano L; Beltrame, Gabriela M; Calegari, Daiane; Batista, Cibele B; Blaser, Rachel E; Roman Júnior, Walter A; Conterato, Greicy M M; Piato, Angelo L; Zanatta, Leila; Magro, Jacir Dal; Rosemberg, Denis B
Animal behaviour is the interaction between environment and an individual organism, which also can be influenced by its neighbours. Variations in environmental conditions, as those caused by contaminants, may lead to neurochemical impairments altering the pattern of the behavioural repertoire of the species. Atrazine (ATZ) is an herbicide widely used in agriculture that is frequently detected in surface water, affecting non-target species. The zebrafish is a valuable model organism to assess behavioural and neurochemical effects of different contaminants since it presents a robust behavioural repertoire and also all major neurotransmitter systems described for mammalian species. The goal of this study was to evaluate the effects of subchronic ATZ exposure in defensive behaviours of zebrafish (shoaling, thigmotaxis, and depth preference) using the split depth tank. Furthermore, to investigate a putative role of cholinergic signalling on ATZ-mediated effects, we tested whether this herbicide alters acetylcholinesterase (AChE) activity in brain and muscle preparations. Fish were exposed to ATZ for 14days and the following groups were tested: control (0.2% acetone) and ATZ (10 and 1000?g/L). The behaviour of four animals in the same tank was recorded for 6min and biological samples were prepared. Our results showed that 1000?g/L ATZ significantly increased the inter-fish distance, as well as the nearest and farthest neighbour distances. This group also presented an increase in the shoal area with decreased social interaction. No significant differences were detected for the number of animals in the shallow area, latency to enter the shallow and time spent in shallow and deep areas of the apparatus, but the ATZ 1000 group spent significantly more time near the walls. Although ATZ did not affect muscular AChE, it significantly reduced AChE activity in brain. Exposure to 10?g/L ATZ did not affect behaviour or AChE activity. These data suggest that ATZ impairs defensive behaviours of zebrafish, which could be related to its action on brain cholinergic neurotransmission. Moreover, the use of the split depth tank could be an alternative strategy to assess group behaviour and depth preference after exposure to chemical compounds. PMID:24893294
Noxious stimulation in children receiving general anaesthesia evokes an increase in delta frequency brain activity.
Hartley, Caroline; Poorun, Ravi; Goksan, Sezgi; Worley, Alan; Boyd, Stewart; Rogers, Richard; Ali, Tariq; Slater, Rebeccah
More than 235,000 children/year in the UK receive general anaesthesia, but it is unknown whether nociceptive stimuli alter cortical brain activity in anaesthetised children. Time-locked electroencephalogram (EEG) responses to experimental tactile stimuli, experimental noxious stimuli, and clinically required cannulation were examined in 51 children (ages 1-12 years) under sevoflurane monoanaesthesia. Based on a pilot study (n=12), we hypothesised that noxious stimulation in children receiving sevoflurane monoanaesthesia would evoke an increase in delta activity. This was tested in an independent sample of children (n=39), where a subset (n=11) had topical local anaesthetic applied prior to stimulation. A novel method of time-locking the stimuli to the EEG recording was developed using an event detection interface and high-speed camera. Clinical cannulation evoked a significant increase (34.2 ± 8.3%) in delta activity (P=0.042), without concomitant changes in heart rate or reflex withdrawal, which was not observed when local anaesthetic was applied (P=0.30). Experimental tactile (P=0.012) and noxious (P=0.0099) stimulation also evoked significant increases in delta activity, but the magnitude of the response was graded with stimulus intensity, with the greatest increase evoked by cannulation. We demonstrate that experimental and clinically essential noxious procedures, undertaken in anaesthetised children, alter the pattern of EEG activity, that this response can be inhibited by local anaesthetic, and that this measure is more sensitive than other physiological indicators of nociception. This technique provides the possibility that sensitivity to noxious stimuli during anaesthesia could be investigated in other clinical populations. PMID:25218826
Action of a modulated electromagnetic field on experimentally evoked epileptiform brain activity in rats
G. D. Antimonii; R. A. Salamov
The effect of a modulated electromagnetic field (MEMF) on experimentally evoked epileptiform activity of brain structures was studied in rats. Exposure to an MEMF with modulation frequencies of 2–30 Hz was shown to induce depression of paroxysmal brain electrical activity in 41% of experiments. Marked weakening of epileptiform activity was observed in 23% of experiments and potentiation in 10.1%. In
Sexual Differentiation of Aromatase Activity in the Rat Brain: Effects of Perinatal Steroid Exposure
Androgens regulate aromatase activity in the medial preoptic area and other components of the brain circuit that mediates male sexual behavior. The levels of aromatase activity within these brain regions are greater in males than in females. As the activation of copulation requires aromatization of testosterone to estradiol, this quantitative enzymatic difference between sexes could contribute to the greater behavioral
Adolescents at Risk for Alcohol Abuse Demonstrate Altered Frontal Lobe Activation during Stroop Performance
Silveri, Marisa M.; Rogowska, Jadwiga; McCaffrey, Alexandra; Yurgelun-Todd, Deborah A.
Background Children and adolescents, family history positive (FH+) for alcoholism, exhibit differences in brain structure and functional activation when compared to family history negative (FH-) counterparts. Given that frontal brain regions, and associated reciprocal connections with limbic structures, undergo the most dramatic maturational changes during adolescence, the objective of this study was to compare functional brain activation during a frontally-mediated test of response inhibition in 32 adolescents separated into low-risk (FH-) and high-risk (FH+) groups. Methods Functional magnetic resonance (fMRI) blood oxygen level dependent (BOLD) data were acquired at 1.5 Tesla during performance of Stroop Color Naming, Word Reading and Interference. Preprocessing and statistical analyses, covaried for age, were conducted in SPM99 using a search territory that included superior, middle, and inferior frontal gyri (trigone region), anterior cingulate gyrus, and left and right amygdala. Results Significantly greater activation in the fronto-limbic search territory was observed in FH+ relative to FH- subjects during Stroop Interference. In addition, a significant regression between brain activation and family history density was observed, with a greater density being associated with increased activation in regions including middle frontal gyrus (BA9) and cingulate gyrus (BA24). Conclusions These data demonstrate a significant influence of FH status on brain activation during the performance of a response inhibition task, perhaps reflecting a neurobiological vulnerability associated with FH status that may include reduced neuronal efficiency and/or recruitment of additional neuronal resources. These findings are important given that the adolescent developmental period is already associated with reduced inhibitory capacity, even prior to the onset of alcohol use. PMID:21073483
Recovery of brain and plasma cholinesterase activities in ducklings exposed to organophosphorus pesticides
Fleming, W.J.
Brain and plasma cholinesterase (ChE) activities were determined for mallard ducklings (Anas platyrhynchos) exposed to dicrotophos and fenthion. Recovery rates of brain ChE did not differ between ducklings administered a single oral dose vs. a 2-week dietary dose of these organophosphates. Exposure to the organophosphates, followed by recovery of brain ChE, did not significantly affect the degree of brain ChE inhibition or the recovery of ChE activity at a subsequent exposure. Recovery of brain ChE activity followed the general model Y = a + b(logX) with rapid recovery to about 50% of normal, followed by a slower rate of recovery until normal ChE activity levels were attained. Fenthion and dicrotophos-inhibited brain ChE were only slightly reactivated in vitro by pyridine-2-aldoxime methiodide, which suggested that spontaneous reactivation was not a primary method of recovery of ChE activity. Recovery of brain ChE activity can be modeled for interpretation of sublethal inhibition of brain ChE activities in wild birds following environmental applications of organophosphates. Plasma ChE activity is inferior to brain ChE activity for environmental monitoring, because of its rapid recovery and large degree of variation among individuals.
Microglial activation induced by brain trauma is suppressed by post-injury treatment with a PARP inhibitor
brain devoid of NeuN staining (because both astrocytes andand astrocyte activation. (A) Coronal rat brain sectionsAstrocyte, Behavioral, Forelimb, Inflammation, Microglia, Minocycline, Poly(ADP-ribose) polymerase, trau- matic brain
Brain phospholipid arachidonic acid half-lives are not altered following 15 weeks of N-3 polyunsaturated fatty acid adequate or deprived diet
Green, Joshua T.; Liu, Zhen; Bazinet, Richard P.
Previous studies have infused radiolabeled arachidonic acid (AA) into rat brains and followed AA esterification into phospholipids for up to 24 h; however, the half-life of AA in rat brain phospholipids is unknown. Eighteen day old rats were fed either an n-3 PUFA adequate or deprived diet for 15 weeks. Following the 15 weeks, 40 µCi of [3H] AA was injected intracerebroventricularly into the right lateral ventricle using stereotaxic surgery and returned to their dietary treatment. From 4–120 days after [3H] AA administration, brains were collected for chemical analyses. The half-life of AA in rat brain phospholipids was 44 ± 4 days for the n-3 PUFA adequate group and 46 ± 4 days for the n-3 PUFA deprived group, which closely approximates the predicted half-life previously reported, based on the rate of entry from the plasma unesterified pool, suggesting the plasma unesterified pool is a major contributor to brain uptake of AA. Furthermore, unlike a previous report in which the half-life of brain phospholipid docosahexaenoic acid (DHA) was increased in n-3 PUFA deprived rats, n-3 PUFA deprivation did not significantly alter the AA half-life, suggesting different mechanisms exist to maintain brain concentrations of AA and DHA. PMID:19661256
Altered spontaneous activity in anisometropic amblyopia subjects: revealed by resting-state FMRI.
Lin, Xiaoming; Ding, Kun; Liu, Yong; Yan, Xiaohe; Song, Shaojie; Jiang, Tianzi
Amblyopia, also known as lazy eye, usually occurs during early childhood and results in poor or blurred vision. Recent neuroimaging studies have found cortical structural/functional abnormalities in amblyopia. However, until now, it was still not known whether the spontaneous activity of the brain changes in amblyopia subjects. In the present study, regional homogeneity (ReHo), a measure of the homogeneity of functional magnetic resonance imaging signals, was used for the first time to investigate changes in resting-state local spontaneous brain activity in individuals with anisometropic amblyopia. Compared with age- and gender-matched subjects with normal vision, the anisometropic amblyopia subjects showed decreased ReHo of spontaneous brain activity in the right precuneus, the left medial prefrontal cortex, the left inferior frontal gyrus, and the left cerebellum, and increased ReHo of spontaneous brain activity was found in the bilateral conjunction area of the postcentral and precentral gyri, the left paracentral lobule, the left superior temporal gyrus, the left fusiform gyrus, the conjunction area of the right insula, putamen and the right middle occipital gyrus. The observed decreases in ReHo may reflect decreased visuo-motor processing ability, and the increases in ReHo in the somatosensory cortices, the motor areas and the auditory area may indicate compensatory plasticity in amblyopia. PMID:22937041
Altered Spontaneous Activity in Anisometropic Amblyopia Subjects: Revealed by Resting-State fMRI
Lin, Xiaoming; Ding, Kun; Liu, Yong; Yan, Xiaohe; Song, Shaojie; Jiang, Tianzi
Amblyopia, also known as lazy eye, usually occurs during early childhood and results in poor or blurred vision. Recent neuroimaging studies have found cortical structural/functional abnormalities in amblyopia. However, until now, it was still not known whether the spontaneous activity of the brain changes in amblyopia subjects. In the present study, regional homogeneity (ReHo), a measure of the homogeneity of functional magnetic resonance imaging signals, was used for the first time to investigate changes in resting-state local spontaneous brain activity in individuals with anisometropic amblyopia. Compared with age- and gender-matched subjects with normal vision, the anisometropic amblyopia subjects showed decreased ReHo of spontaneous brain activity in the right precuneus, the left medial prefrontal cortex, the left inferior frontal gyrus, and the left cerebellum, and increased ReHo of spontaneous brain activity was found in the bilateral conjunction area of the postcentral and precentral gyri, the left paracentral lobule, the left superior temporal gyrus, the left fusiform gyrus, the conjunction area of the right insula, putamen and the right middle occipital gyrus. The observed decreases in ReHo may reflect decreased visuo-motor processing ability, and the increases in ReHo in the somatosensory cortices, the motor areas and the auditory area may indicate compensatory plasticity in amblyopia. PMID:22937041
Alterations in brain connectivity in three sub-regions of the anterior cingulate cortex in heroin-dependent individuals: Evidence from resting state fMRI.
Zhang, Y; Gong, J; Xie, C; Ye, E M; Jin, X; Song, H; Yang, Z; Shao, Y
Previous studies that utilized task-based approaches have demonstrated that the chronic use of heroin is associated with altered activity of the anterior cingulate cortex (ACC). However, few studies have focused on examining the variation in resting-state functional connectivity in heroin-dependent individuals, which might help further understanding the mechanisms underlying heroin addiction. Due to the structural and functional heterogeneity of the ACC, we systematically mapped the resting-state functional connectivity patterns of three sub-regions of the ACC in heroin-dependent individuals, wondered whether the partition of three sub-regions of the ACC is feasible in heroin-dependent individuals, and identified how heroin affected the correlated activities among three sub-regions of the ACC using resting-state functional magnetic resonance imaging (fMRI). In the present study, fMRI data were acquired from 21 heroin-dependent individuals (Her group) and 15 non-addicted controls (CN group). Compared to controls, there were reduced functional connectivities in the dorsal ACC (dACC) and rostral ACC (rACC) networks with different areas of the dorsal striatum (the caudate and the putamen) in the Her group. Meanwhile, there exhibited an inverted alteration of pattern for orbital frontal cortex (OFC) and superior frontal gyrus (SFG) in the functional connectivity network with the dACC and subcallosal ACC (sACC), and a different alteration of the cerebellum and the amygdala in the functional connectivity network with the rACC and the sACC. In addition, we also found reduced connectivities between dACC and rACC, as well as reduced connectivities between sACC and dACC. Our findings of variations of functional connectivities in three sub-regions of ACC in Her group implied that these sub-regions of the ACC together with other key brain areas (such as dorsal striatum, OFC, SFG, cerebellum, amygdale, etc.) might potentially play independent and/or overlapping roles in heroin addiction, which might indicate the potential direction of future research. PMID:25446365
The role of the extrapersonal brain systems in religious activity.
Previc, Fred H
The neuropsychology of religious activity in normal and selected clinical populations is reviewed. Religious activity includes beliefs, experiences, and practice. Neuropsychological and functional imaging findings, many of which have derived from studies of experienced meditators, point to a ventral cortical axis for religious behavior, involving primarily the ventromedial temporal and frontal regions. Neuropharmacological studies generally point to dopaminergic activation as the leading neurochemical feature associated with religious activity. The ventral dopaminergic pathways involved in religious behavior most closely align with the action-extrapersonal system in the model of 3-D perceptual-motor interactions proposed by . These pathways are biased toward distant (especially upper) space and also mediate related extrapersonally dominated brain functions such as dreaming and hallucinations. Hyperreligiosity is a major feature of mania, obsessive-compulsive disorder, schizophrenia, temporal-lobe epilepsy and related disorders, in which the ventromedial dopaminergic systems are highly activated and exaggerated attentional or goal-directed behavior toward extrapersonal space occurs. The evolution of religion is linked to an expansion of dopaminergic systems in humans, brought about by changes in diet and other physiological influences. PMID:16439158
Influenza matrix protein 2 alters CFTR expression and function through its ion channel activity
Londino, James D.; Lazrak, Ahmed; Jurkuvenaite, Asta; Collawn, James F.; Noah, James W.
The human cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-activated chloride (Cl?) channel in the lung epithelium that helps regulate the thickness and composition of the lung epithelial lining fluid. We investigated whether influenza M2 protein, a pH-activated proton (H+) channel that traffics to the plasma membrane of infected cells, altered CFTR expression and function. M2 decreased CFTR activity in 1) Xenopus oocytes injected with human CFTR, 2) epithelial cells (HEK-293) stably transfected with CFTR, and 3) human bronchial epithelial cells (16HBE14o?) expressing native CFTR. This inhibition was partially reversed by an inhibitor of the ubiquitin-activating enzyme E1. Next we investigated whether the M2 inhibition of CFTR activity was due to an increase of secretory organelle pH by M2. Incubation of Xenopus oocytes expressing CFTR with ammonium chloride or concanamycin A, two agents that alkalinize the secretory pathway, inhibited CFTR activity in a dose-dependent manner. Treatment of M2- and CFTR-expressing oocytes with the M2 ion channel inhibitor amantadine prevented the loss in CFTR expression and activity; in addition, M2 mutants, lacking the ability to transport H+, did not alter CFTR activity in Xenopus oocytes and HEK cells. Expression of an M2 mutant retained in the endoplasmic reticulum also failed to alter CFTR activity. In summary, our data show that M2 decreases CFTR activity by increasing secretory organelle pH, which targets CFTR for destruction by the ubiquitin system. Alteration of CFTR activity has important consequences for fluid regulation and may potentially modify the immune response to viral infection. PMID:23457187
Kinetic Analysis of Mouse Brain Proteome Alterations Following Chikungunya Virus Infection before and after Appearance of Clinical Symptoms
Fraisier, Christophe; Koraka, Penelope; Belghazi, Maya; Bakli, Mahfoud; Granjeaud, Samuel; Pophillat, Matthieu; Lim, Stephanie M.; Osterhaus, Albert; Martina, Byron; Camoin, Luc; Almeras, Lionel
Recent outbreaks of Chikungunya virus (CHIKV) infection have been characterized by an increasing number of severe cases with atypical manifestations including neurological complications. In parallel, the risk map of CHIKV outbreaks has expanded because of improved vector competence. These features make CHIKV infection a major public health concern that requires a better understanding of the underlying physiopathological processes for the development of antiviral strategies to protect individuals from severe disease. To decipher the mechanisms of CHIKV infection in the nervous system, a kinetic analysis on the host proteome modifications in the brain of CHIKV-infected mice sampled before and after the onset of clinical symptoms was performed. The combination of 2D-DIGE and iTRAQ proteomic approaches, followed by mass spectrometry protein identification revealed 177 significantly differentially expressed proteins. This kinetic analysis revealed a dramatic down-regulation of proteins before the appearance of the clinical symptoms followed by the increased expression of most of these proteins in the acute symptomatic phase. Bioinformatic analyses of the protein datasets enabled the identification of the major biological processes that were altered during the time course of CHIKV infection, such as integrin signaling and cytoskeleton dynamics, endosome machinery and receptor recycling related to virus transport and synapse function, regulation of gene expression, and the ubiquitin-proteasome pathway. These results reveal the putative mechanisms associated with severe CHIKV infection-mediated neurological disease and highlight the potential markers or targets that can be used to develop diagnostic and/or antiviral tools. PMID:24618821
Voluntary exercise prior to traumatic brain injury alters miRNA expression in the injured mouse cerebral cortex
Miao, W.; Bao, T.H.; Han, J.H.; Yin, M.; Yan, Y.; Wang, W.W.; Zhu, Y.H.
MicroRNAs (miRNAs) may be important mediators of the profound molecular and cellular changes that occur after traumatic brain injury (TBI). However, the changes and possible roles of miRNAs induced by voluntary exercise prior to TBI are still not known. In this report, the microarray method was used to demonstrate alterations in miRNA expression levels in the cerebral cortex of TBI mice that were pretrained on a running wheel (RW). Voluntary RW exercise prior to TBI: i) significantly decreased the mortality rate and improved the recovery of the righting reflex in TBI mice, and ii) differentially changed the levels of several miRNAs, upregulating some and downregulating others. Furthermore, we revealed global upregulation of miR-21, miR-92a, and miR-874 and downregulation of miR-138, let-7c, and miR-124 expression among the sham-non-runner, TBI-non-runner, and TBI-runner groups. Quantitative reverse transcription polymerase chain reaction data (RT-qPCR) indicated good consistency with the microarray results. Our microarray-based analysis of miRNA expression in mice cerebral cortex after TBI revealed that some miRNAs such as miR-21, miR-92a, miR-874, miR-138, let-7c, and miR-124 could be involved in the prevention and protection afforded by voluntary exercise in a TBI model. PMID:25760028
Oscillatory brain activity in vegetative and minimally conscious state during a sentence comprehension task.
Schabus, Manuel; Pelikan, Christoph; Chwala-Schlegel, Nicole; Weilhart, Katharina; Roehm, Dietmar; Donis, Johann; Michitsch, Gabriele; Pichler, Gerald; Klimesch, Wolfgang
Patients with altered states of consciousness continue to constitute a major challenge in terms of clinical assessment, treatment and daily management. Furthermore, the exploration of brain function in severely brain-damaged patients represents a unique lesional approach to the scientific study of consciousness. Electroencephalography is one means of identifying covert behaviour in the absence of motor activity in these critically ill patients. Here we focus on a language processing task which assesses whether vegetative (n=10) and minimally conscious state patients (n=4) (vs control subjects, n=14) understand semantic information on a sentence level ("The opposite of black is... white/yellow/nice"). Results indicate that only MCS but not VS patients show differential processing of unrelated ("nice") and antonym ("white") words in the form of parietal alpha (10-12Hz) event-related synchronization and desynchronization (ERS/ERD), respectively. Controls show a more typical pattern, characterized by alpha ERD in response to unrelated words and alpha ERS in response to antonyms. PMID:21693086
P-glycoprotein Inhibition Increases the Brain Distribution and Antidepressant-Like Activity of Escitalopram in Rodents
O'Brien, Fionn E; O'Connor, Richard M; Clarke, Gerard; Dinan, Timothy G; Griffin, Brendan T; Cryan, John F
Despite the clinical prevalence of the antidepressant escitalopram, over 30% of escitalopram-treated patients fail to respond to treatment. Recent gene association studies have highlighted a potential link between the drug efflux transporter P-glycoprotein (P-gp) and response to escitalopram. The present studies investigated pharmacokinetic and pharmacodynamic interactions between P-gp and escitalopram. In vitro bidirectional transport studies revealed that escitalopram is a transported substrate of human P-gp. Microdialysis-based pharmacokinetic studies demonstrated that administration of the P-gp inhibitor cyclosporin A resulted in increased brain levels of escitalopram without altering plasma escitalopram levels in the rat, thereby showing that P-gp restricts escitalopram transport across the blood–brain barrier (BBB) in vivo. The tail suspension test (TST) was carried out to elucidate the pharmacodynamic impact of P-gp inhibition on escitalopram effect in a mouse model of antidepressant activity. Pre-treatment with the P-gp inhibitor verapamil enhanced the response to escitalopram in the TST. Taken together, these data indicate that P-gp may restrict the BBB transport of escitalopram in humans, potentially resulting in subtherapeutic brain concentrations in certain patients. Moreover, by verifying that increasing escitalopram delivery to the brain by P-gp inhibition results in enhanced antidepressant-like activity, we suggest that adjunctive treatment with a P-gp inhibitor may represent a beneficial approach to augment escitalopram therapy in depression. PMID:23670590
Brain projects think big When you read these words, hundreds of million of nerve cells are electrically and chemically active in your brain. This