The mechanistic analyses on the effects of ethano Ion the maturation and the differentiation of neural stem cells in the primordium of cerebral cortex.

乙醇是一种强效致痛剂，可导致中枢神经系统先天畸形。本研究的结果表明，乙醇改变了发育中的新皮质脑室带顶面神经前体细胞的有丝分裂分裂面方向。免疫组织化学分析还表明，GABA_A受体的α4亚单位在胚胎10岁的神经前体细胞中已经表达。GABA和牛磺酸是GABA_A受体的内源性激动剂，也存在于发育中的新皮质中，在E10以后的各个阶段都有特定的层流模式。这些结果表明，胎儿接触乙醇扰乱了通过GABA_A受体对有丝分裂纺锤体方向的调节，这可能导致中枢神经系统的先天性畸形。

Ethanol is a potent tetatogen to induce congenital malformation in the central nervous system. The results of this study showed that ethanol alters mitotic cleavage plane orientation of the neural progenitors at the apical surface of the ventricular zone in the developing neocortex. Immunohistochemical analyses also showed that the alpha4 subunit of GABA_A receptors is already expressed in the neural progenitors at E10. GABA and Taurine, the endogenous agonists of GABA_A receptors, are also present in the developing neocortex with specific laminar patterns throughout the stages after E10. These results suggest that fetal exposure to ethanol perturbs the regulation of mitotic spindle orientation via GABA_A receptors, which may result in congenital malformation in the central nervous system.