Title: Mycotoxins - an overview | ScienceDirect Topics
Headings: Mycotoxins
Mycotoxins
Climatic Factors Under the Tropics
3.5.6 Fungal Proliferation Under the Tropics
Developmental Toxicity Within the Central Cholinergic Nervous System
V Cholinergic Mechanisms of Developmental Neurotoxicity
Neuroactive steroids and metabolic axis
1.2 Zearalenone (Zea)
Why does Finland have the highest dementia mortality rate? Environmental factors may be generalizable
5 Suggested evaluation of the hypothesis
Therapeutic Strategies for Mitochondrial Disorders
Avoidance of mitochondrion-toxic agents
Voltage- and calcium-gated ion channels of neurons in the vertebrate retina
2.3.2 Ca2+- activated K+ channels
Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides
2.4 Antioxidant peptides

Content: The level of cholinergic neurotransmission throughout prenatal and postnatal development exerts a significant influence on not only axonal outgrowth and pathfinding, but also the formation and refinement of neural networks in the developing brain,14,77,86 which includes defining the ratio of excitatory to inhibitory neurotransmission 86 and the rate of neurogenesis in the developing and adult brain. 77 Developmental neurotoxicants that alter ACh levels can interfere with these neurodevelopmental processes, as exemplified by aflatoxin, a mycotoxin found in contaminated human and animal cereal-based foodstuffs. One of the most prevalent aflatoxins, aflatoxin B1, and its metabolites, aflatoxin M1 and aflatoxicol, readily cross the placenta and are transferred into milk. Preclinical studies in a rat model have shown that developmental exposures to sublethal concentrations of aflatoxin B1 in the maternal diet impairs locomotor coordination and causes learning deficits in exposed offspring.87–89 These behavioral changes have been linked to decreased hippocampal neurogenesis secondary to suppression of cholinergic signals on hilar GABAergic interneurons and release of BDNF from granule cells.89 Similarly, decreased cholinergic signaling caused by developmental exposure to lead (Pb) can trigger cholinergic neuronal cell death in the medial septal area of the brain, resulting in long-lasting behavioral deficits.90–92
ACh receptors exert regulatory influence on multiple neurodevelopmental events 14 and reduced cholinergic innervation during development results in reduced cortical thickness and dendritic abnormalities in the adult brain. 77 Nicotinic receptors play a critical role in promoting cell division, differentiation, and synaptogenesis, and in regulating neurotransmitter release, with much of this activity attributed to α7 nicotinic receptors.14,77 Spontaneous nicotinic excitation in the rodent brain during a brief developmental window in the first postnatal weeks is required for the developmental shift of GABA receptors from depolarizing to hyperpolarizing.77
Relative to nicotinic receptors, much less is known about the role of muscarinic receptors in the developing brain, although studies of muscarinic receptor agonists and antagonists indicate that these receptors contribute to effects of ACh on cell proliferation, differentiation and survival in the developing brain.14 Muscarinic receptors appear to play a predominant role in mediating the effects of ACh on neurite outgrowth. The axon inhibitory effects of ACh in thalamic explant cultures from GD 14 mice are blocked by nicotinic and muscarinic receptor antagonists, but the latter are more potent.83 Conversely, M1 muscarinic receptor agonists stimulate axonal outgrowth in primary cultures of rat hippocampal pyramidal neurons via activation of protein kinase C and extracellular signal-related kinase 1/2.93 M3 muscarinic receptor–dependent mechanisms mediate the neurite-stimulating influence of astrocytes. Coculture of rat hippocampal neurons with astrocytes pretreated with the cholinergic agonist carbachol enhances neurite outgrowth, presumably via secretion of permissive factors.94
Cholinergic receptor activation also plays an important role in regulating gene expression, which is critical for normal brain development. Signaling via nicotinic or muscarinic receptors can increase phosphorylation of the transcription factor cAMP response element binding protein (CREB), which activates gene transcription (Fig. 16.2 ). 14 CREB regulates the transcription of a large number of genes 95 and CREB-responsive genes are involved in multiple aspects of neurodevelopment, including neurogenesis, cell survival, axonal and dendritic growth and plasticity, and synaptogenesis.