Study on the cognitive and behavioral consequences of prenatal or early developmental exposure of the brain to ethanol

点击翻译按钮获取中文摘要

The purpose of this study was to elucidate the relationship between prenatal or early developmental exposure of the brain to ethanol and cognitive and behavioral disturbances observed after adolescence. We assumed such disturbances in behavior or cognition might be caused by alternation of neural network which was already started at prenatal or early developmental phase. Because neural stem cells (NSCs) play a pivotal role in the development and maturation of the central nervous system, it seems to be important to understand the effect of ethanol on underlying mechanisms that regulate NSC differentiation in the developing brain. In this study, we investigated the effects of ethanol on differentiation of NSC to neural cells and glial cells. To clarify the underlying mechanisms of the effects, we examined the signal transduction system involved in the regulation of NSC differentiation.The results were followings ; 1)Ethanol inhibited NSC differentiation at concentrations much lower than what compromised neuronal survival. 2)Ethanol exposure increased astrocytic and oligocytic differentiation at the concentration as same above. 3)Ethanol-induced differential inhibition was reduced by both IGF-1 and BDNF. 4)Western blot analysis revealed that ethanol suppressed phosphorylation of ERK without affecting expression of total ERK. 5)Ethanol enhanced NRSF binding activity measured by the method based on the principal of electrophoretic mobility sift assay.These results implicated that physiological concentration of ethanol affects on actively differentiated NSC in the developing brain, then these cause the alteration of neural network system. This study is possible to make a contribution to elucidation of underlying mechanisms of the harmful consequences of drinking during pregnancy.