neurotrophin-3 ( nt-3 ) belongs to the neurotrophin family , which   includes , among others , 
 the nerve growth factor and the brain - derived neurotrophic 
 factor ( bdnf ) . neurotrophins exert antiapoptotic activities in 
 neurons   and are implicated in higher neuronal functions 
  and neurotransmitter 
 expression . therefore , 
 neurotrophins may play important roles in antenatal and postnatal 
 brain development . in addition , neurotrophins are involved in 
 the immune response [ 5 , 
 6 , 7 , 
 8 ] . moreover , nerve growth 
 factor , bdnf , and nt-3 act 
 on tyrosine kinase a , b , and c receptors , respectively . it has 
 recently been reported that in neonatal age circulating 
 neurotrophin levels could reflect the degree of neuronal maturity 
 , since , at this age , due to the immature blood - brain 
 barrier , neurotrophin blood levels may also represent 
 concentrations in the cns . the flt3 receptor ( flt3 ) is a member of the class iii receptor 
 tyrosine kinases . related members of this family of 
 receptors together with their respective ligands have been shown 
 to control numerous distinct stages of hematopoiesis [ 11 , 12 ] . recently , regions of the brain have been shown to harbor neural 
 stem / progenitor cells that retain the capacity to proliferate and 
 to give rise to new cells throughout the lifetime of an animal 
 [ 10 , 13 ] . thus , they generate neurons , oligodendrocytes , 
 astrocytes , but also retain the ability to repopulate 
 hematopoietic systems of irradiated animals   and to give 
 rise to multiple tissue types when grown in the presence of 
 embryonic stem cells . on the other hand , hematopoietic 
 stem cells have been shown to give rise to neurons , when 
 transplanted into mice [ 16 , 17 , 
 18 , 19 ] . in this respect , many 
 studies have confirmed the presence of flt3 mrna in nervous tissue 
 [ 20 , 21 ] . this study was based on the hypothesis that a possible interaction 
 between hematopoietic and neuronal activity in the central 
 nervous system , possibly also representing the state of maturity , 
 might be reflected in the periphery . thus , we aimed to determine 
 circulating levels of nt-3 and flt3 in full - term neonates and 
 correlate these levels with gestational age , gender , and mode of 
 delivery . the study was approved by the ethics committee of our teaching 
 hospital and informed consent was obtained from participating 
 mothers . the study included 30 healthy , infection - free , 
 nonsmoking parturients ( mean age : 25.6  3.4 , range : 2040 
 years ) and their healthy neonates appropriate for gestational 
 age and born after single uncomplicated pregnancy and delivery . complete blood 
 count and c - reactive protein were within normal ranges in all 
 newborns . all infants received breast milk . developed jaundice 
 required phototherapy treatment in 5 infants . thus , 
 blood was taken from ( a ) the mothers ( ms ) before delivery ( at the 
 first stage of labor , or before receiving anesthesia in cases of 
 elective cesarean section ) , ( b ) the doubly   clamped 
 umbilical cord ( uc ) at delivery ( uc representing fetal state ) , 
 and   the neonates ( c ) on the first ( n1 ) and ( d ) fourth days 
 ( n4 ) . the blood was collected in pyrogen - free tubes ; 
 following centrifugation the supernatant serum and edta plasma 
 were kept frozen at 80  c until assay . nt-3 and flt3 
 were determined in serum and edta - plasma , respectively , by enzyme 
 immunoassays ( r&d systems minneapolis , minn 55413 , catalogue 
 numbers dy 267 and dfk 00 , respectively ) . the minimum detectable 
 concentration , intraassay and interassay coefficients of 
 variations were for nt-3 1  pg / ml , 8.7% and 14.9% , and 
 for flt3 less than 7 variables were checked for normality of their distribution by 
 kolmogorov - smirnov one - sample test . the circulating nt-3 and flt3 levels in ms , uc , n1 , and n4 are 
 presented in table 2 . statistically significant 
 differences were found in nt-3 levels between ms and n4 
 ( p = .03 ) , uc and n4 ( p = .03 ) , and n1 
 and n4 ( p = .03 ) . on the 
 other hand in addition , ms nt-3 , as 
 well as uc nt-3 levels , positively correlated with respective 
 flt3 levels ( p = .003 , and p = .03 ) . no correlation with 
 gender , gestational age , or mode of delivery was found for either 
 nt-3 or flt3 . the results of this study indicate that nt-3 serum concentrations 
 rise significantly on the forth day of life , from the low levels 
 encountered in the umbilical cord and on the first postnatal day . the significant increase of nt-3 on the fourth postnatal day may 
 indicate its secretion from the nervous and immune systems of the 
 neonate , as a result of exposure to various stimuli soon after 
 birth . respectively , in a recent study we demonstrated that the 
 bdnf circulating levels increased significantly in the postnatal 
 period , as compared to the fetal levels . it has been 
 stated that neurotrophins are important for the physiological 
 function of the peripheral as well as the central nervous system , 
 contributing to developmental maturity of the cortex and 
 plasticity of the synapses , leading to the refinement of 
 connections . in addition , previous studies reported 
 that neurotrophins are produced , stored , and released by various 
 immune cells , and elevated plasma levels are found in 
 inflammatory , autoimmune , and allergic diseases . transition of the infant to extrauterine life , where he or she is 
 exposed to a variety of antigenic stimuli , including 
 feeding , might be responsible for the postnatal 
 significant increase of nt-3 . furthermore , it has been reported 
 that the elevation of neurotrophins might also be a consequence of 
 proinflammatory cytokines , the production of which 
 then again is influenced by the former . accordingly , 
 we have previously demonstrated   a significant increase 
 in circulating levels of the proinflammatory cytokines 
 interleukin-1 , interleukin-6 , and tumor necrosis 
 factor- in healthy neonates soon after birth . lastly , one should consider a third parameter possibly implicated 
 in the increased postnatal circulating nt-3 levels : its secretion 
 by vascular endothelial cells .   the latter multiply and 
 migrate , contributing to the formation of new blood vessels from 
 preexisting ones ( angiogenesis ) , when rapid growth and 
 development is taking place , particularly in the third 
 trimester of pregnancy , and to a lesser extent in 
 neonatal life . it has been previously described that many cytokines are shared 
 by the haematopoietic and nervous systems and they exert 
 different functions in different contexts . nerve growth 
 factor can act as a colony - stimulating factor , as it stimulates 
 immature erythroleukemic cell lines and bone - marrow - derived 
 precursor cells to proliferate . flt3 is most robustly 
 expressed on differentiated postmitotic neurons , whereas in the 
 hematopoietic system , immature cells preferentially express flt3 . the lack of increased flt3 levels in fetal and 
 neonatal samples , according to this study , could possibly be 
 attributed to the fact that examined peripheral blood did not 
 contain immature hematopoietic cells , as neonates were full term 
 and infection free . on the other hand , it has been shown that 
 flt3 does not play a role as a trophic factor during the early 
 stages of development within the central nervous system . our finding that ms and uc nt-3 levels , positively correlated 
 with ms and uc flt3 levels , respectively , could be explained in 
 parallel with the ability of flt3 to synergize with ngf , thus to 
 enhance the competence of neurons to respond to neurotrophins 
 . however , a further explanation could take into account 
 the interactions of the nervous and immune systems , particularly 
 under stress situations , as it happens in labor and delivery . in conclusion , circulating nt-3 levels increase during 
 the early neonatal life . however , circulating flt3 levels do not 
 seem to behave accordingly , although these two substances 
 probably synergize .
our aim is to determine  in 30 healthy full - term 
 infants and their mothers  circulating levels of neurotrophin-3 
 ( nt-3 ) ( important for antenatal and postnatal brain development 
 and implicated in the immune response ) and flt3 tyrosine kinase 
 receptor ( flt3 ) ( controlling hematopoiesis and found in the 
 nervous tissue ) , in the fetal and neonatal life . 
 nt-3 levels , in 
 contrast to flt3 ones , increased significantly on the fourth 
 postnatal day in relation to the low levels found in the mother , 
 fetus , and day 1 neonate ( p = .03 , respectively ) . 
 maternal and 
 umbilical nt3 levels positively correlated with respective flt3 
 levels ( p = .003 and p = .03 ) . circulating nt-3 levels increased 
 in early neonatal life , possibly due to exposure to various 
 stimuli soon after birth . 
 flt3 levels do not seem to behave 
 accordingly , although these two substances probably synergize .