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

乙醇是诱发中枢神经系统先天性畸形的强毒性物质。本研究的结果表明，乙醇改变了发育中的新皮质中脑室区顶面的神经祖细胞的有丝分裂面方向。免疫组织化学分析也表明，GABA_A受体α 4亚基在E10时已经在神经祖细胞中表达。GABA_A受体的内源性激动剂GABA和牛磺酸也存在于发育中的新皮层中，在E10后的整个阶段具有特定的层状模式。这些结果表明，胎儿暴露于乙醇干扰有丝分裂纺锤体的方向调节通过GABA_A受体，这可能会导致先天性畸形的中枢神经系统。

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.