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

通过扰动神经祖细胞的细胞特性调节分析GABAA受体靶向药物的致畸作用机制

• 批准号: 23791227
• 负责人: TOCHITANI Shiro
• 金额: $ 2.66万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791227/
• 关键词: 先天異常学; 神経前駆細胞; 発生・分化; 脳発達障害; エタノール; GABA_A受容体; 神経幹細胞; GABAA受容体; 大脳新皮質; 細胞分化; 大脳皮質; 催奇形性

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.

胎儿暴露于GABA_A受体激动剂（用作麻醉药物等），常引起脑组织畸形和脑功能损害。本研究结果表明，胎儿暴露于GABA_4受体激动剂可影响神经上皮细胞向放射状胶质细胞的转化以及神经前体细胞产生的神经元亚型，提示这些效应是GABA_4受体作用物质作为中枢神经系统致畸剂的基础。我们的结果还表明，在新皮层发育的早期，牛磺酸可能是GABA_A受体的主要配体，这意味着在发育中的新皮层中，当GABA含量远低于牛磺酸时，发育中的新皮层对GABA_A受体激动剂更敏感。

项目成果

Neurogenesis is regulated by the signals via GABAA receptors in the neural progenitors in the developing cortex.

神经发生受发育皮质神经祖细胞中 GABAA 受体信号的调节。

• 作者: Shiro Tochitani