| Background:IUGR refers to the failure of the fetus to achieve its designated growth potential because of anatomical and/or functional disordersor diseases in the fetal-placental-maternal unit,which appears that a birthweight less than 2 standard deviations(SD)below the median for gestational age.IUGR can cause multiple organs disfunction,in which the central nervous system is the main one.Moreover,it can develpe much more short-term and long-term adverse neural damage.Taurine is one of the most important essential amino acids in the brain and plays a vital role during fetal and neonatal growth and development of the nervous system.Our previous studies showed that antenatal taurine supplementation can significantly increase the taurine contents in IUGR fetal rat brains and thus improves IUGR fetal rat brain development through regulate the protein kinase A(PKA)-cyclic adenosine monophosphate response element protein(cAMP-PKA-CREB)signalpathway.Taurine plays an important role in brain the survival proliferation,differentiation,and adhension of neural stem cells.whether antenatal taurine could improve NSC proliferation in IUGR rat brain via cAMP-PKA-CREB pathway remains unknown.In this study,the effect of antenatal taurine supplements on the expression of the keysignaling molecules of signal pathway were investigated to explore the new mechanisms of antenatal taurine improving NSC proliferation in IUGR rat brain.Methods:A total of 40 pregnant rats were randomly divided into the following three groups:control,IUGR(fed with restricted diet about 40%of normal diet in control group),and IUGR with antenatal taurine supplementation groups(add 300 mg/kg/d taurine from 7 days after conception until natural full-term delivery.).For in vivo,the number FABP-7 positive cells was measured by immunohistochemistry,The expression of FABP-7 and factor-in-signal-pathway 's mRNA and proteins in rat brain tissues were detected by quantitative real time(qRT)-polymerase chain reaction(PCR)and Western blot,respectively.For in vitro,neural stem cells were seprated from the fetal rats in control group and IUGR group.FABP-7 and Nestin were detected in NSC by cyto-immunofluorescence(CIF).CCK8 test and cell number counting were used to detected the NSC proliferation in control group,IUGR group and taurine-treated group with different concentration.The expression of PKA,CaMKII,c-AMP,CREB,p-CREB,BDNF,GDNF,c-jun and c-fos mRNA in NSC of each group were detected by qRT-PCR in control,IUGR,Taurine and aurine+H89 group.Results:Compared with normal control groups both the birth weight and brain weight were significantly decreased in IUGR rats,while antenatal taurine supplementation significantly increased this above IUGR levels(p<0.05).The FABP-7 positive cells in fetal rat brain tissues were decreased in fetal brain tissue from the IUGR group compared with the control group,and increased in Taurine group(p<0.05).The relative expression of FABP-7 mRNA and protein levels in fetal rat brain tissues were decreased in fetal brain tissue from the IUGR group compared with the control group,and increased in Taurine group(p<0.05).The relative mRNA level and protein level of PKA,CaMKII,c-AMP,CREB,p-CREB,BDNF,GDNF,c-jun and c-fos in fetal brain were different significantly from each group(p<0.05).The cell proliferation index and the total number decreased in IUGR group compared with control group,while after adding taurine,especially with 10mM,the cell proliferation index and the total cell number increased significantly(p<0.05).The relative mRNA level of PKA,CaMKII,c-AMP,CREB,p-CREB,BDNF,GDNF,c-jun and c-fos in NSC from each group was significantly different from each group(p<0.05).Conclusion:IUGR damage the proliferation of NSC in fetal brain.Antenatal taurine supplement can improve the proliferation ability of NSC in IUGR fetal brain which is associated with regulating the activity of cAMP-PKA-CREB signal pathway. |
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