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BAX敲除对小鼠大脑皮层和海马星形胶质细胞分布的影响

朱莉芳, 吴晓阳, 刘学, 马良, 张琪, 余子, 贺智娇, 应玥, 张竹天, 潘晓玉, 蔡予琦, 龚玲, 何苗^*

复旦大学脑科学研究院，上海 200032

摘要

星形胶质细胞是大脑中一类高度异质的重要大胶质细胞，不仅在脑的发育和功能中起到重要作用，也参与多种神经病理生理学过程。多项研究表明B淋巴细胞瘤-2相关X蛋白(B-cell lymphoma-2 associated X protein, BAX)依赖性凋亡通路参与调控正常发育过程中脑内神经元的数量与分布，但是对其调控星形胶质细胞的研究则较为匮乏。本文旨在研究BAX是否参与不同脑区星形胶质细胞分布的调控。以纯合子和杂合子BAX敲除小鼠为研究对象，用SOX9免疫荧光染色法检测6周龄小鼠的大脑皮层和海马中星形胶质细胞的密度。结果显示，星形胶质细胞的密度在不同皮层分区之间以及皮层和海马之间存在显著差异，并且BAX敲除导致海马中星形胶质细胞的密度显著降低，皮层中GABA能抑制神经元密度显著升高，而皮层中星形胶质细胞的密度则未受显著影响。以上结果提示，BAX差异调控皮层星形胶质细胞与神经元，也差异调控皮层与海马中的星形胶质细胞。这项研究为了解星形胶质细胞的区域异质性和BAX在大脑发育中的功能提供了重要信息。

关键词： 星形胶质细胞; B淋巴细胞瘤-2相关X蛋白; 皮层; 海马

分类号：Q189

Absence of BAX differentially affects astrocyte density in the mouse cortex and hippocampus

ZHU Li-Fang, WU Xiao-Yang, LIU Xue, MA Liang, ZHANG Qi, YU Zi, HE Zhi-Jiao, YING Yue, ZHANG Zhu-Tian, PAN Xiao-Yu, CAI Yu-Qi, GONG Ling, HE Miao^*

Institutes of Brain Science, Fudan University, Shanghai 200032, China

Abstract

 Astrocytes are a heterogenous group of macroglia present in all regions of the brain and play critical roles in many aspects of brain development, function and disease. Previous studies suggest that the B-cell lymphoma-2 associated X protein (BAX)-dependent apoptosis plays essential roles in regulating neuronal number and achieving optimal excitation/inhibition ratio. The aim of the present paper was to study whether BAX regulates astrocyte distribution in a region-specific manner. Immunofluorescence staining of SOX9 was used to analyze and compare astrocyte density in primary somatosensory cortex, motor cortex, retrosplenial cortex and hippocampus in heterozygous and homozygous BAX knockout mice at age of six weeks when cortical development has finished and glia development has reached a relatively steady state. The results showed that astrocyte density varied significantly among different cortical subdivisions and between cortex and hippocampus. In contrast to the significant increase in GABAergic interneurons, the overall and region-specific astrocyte density remained unchanged in the cortex when BAX was absent. Interestingly, a significant reduction of astrocyte density was observed in the hippocampus of BAX knockout mice. These data suggest that BAX differentially regulates neurons and astrocytes in cortex as well as astrocytes in different brain regions during development. This study provided important information about the regional heterogeneity of astrocyte distribution and the potential contribution of BAX gene during development.

Key words: astrocytes; B-cell lymphoma-2 associated X protein; cortex; hippocampus

收稿日期：2020-05-07　　录用日期：2020-11-04

通讯作者：何苗　　E-mail: hem@fudan.edu.cn

DOI: 10.13294/j.aps.2021.0007

引用本文：

朱莉芳, 吴晓阳, 刘学, 马良, 张琪, 余子, 贺智娇, 应玥, 张竹天, 潘晓玉, 蔡予琦, 龚玲, 何苗. BAX敲除对小鼠大脑皮层和海马星形胶质细胞分布的影响[J]. 生理学报 2021; 73 (1): 1-9.

ZHU Li-Fang, WU Xiao-Yang, LIU Xue, MA Liang, ZHANG Qi, YU Zi, HE Zhi-Jiao, YING Yue, ZHANG Zhu-Tian, PAN Xiao-Yu, CAI Yu-Qi, GONG Ling, HE Miao. Absence of BAX differentially affects astrocyte density in the mouse cortex and hippocampus. Acta Physiol Sin 2021; 73 (1): 1-9 (in Chinese with English abstract).