Analyses on the mechanisms of the teratogenic effectsof GABAA receptor-targeting drugs by way of the perturbation of the regulation of the cellular properties of neural progenitor cells

胎儿暴露于GABA_A受体激动剂，常导致脑组织畸形和脑功能损害，GABA_A受体激动剂被用作麻醉药物等。本研究结果表明，胎儿暴露于gaba_a受体激动剂会影响神经上皮细胞向放射状胶质细胞的转变以及神经祖细胞产生的神经元亚型，这表明这些影响是gaba_a受体作用物质作为中枢神经系统致畸物功能的基础。我们的研究结果还表明，在新皮层发育的早期阶段，牛磺酸可能是GABA_A受体的主要配体，这意味着当GABA_A远低于牛磺酸时，发育中的新皮层对GABA_A受体激动剂更敏感。

Fetal exposure to GABA_A receptor agonists, which are used as anesthetic drugs etc., often causes the malformation of brain tissues and the impairment of brain function. The results of this study showed that fetal exposure to GABA_Areceptor agonists influence the transition from neuroepithelial cells to radial glia and the subtypes of neurons that the neural progenitors produce, suggesting that these effects underlie the functions of GABA_Areceptor-acting substances as teratogens for the central nervous system. Our results also showed that taurine might function as a principal ligand for GABA_A receptors in the early phase of neocortical development, implying that the developing neocortices are more sensitive to GABA_A receptor agonists at these stages when GABA is much less than taurine inthe developing neocortices.