Astrocytes exhibit diverse Ca2+ changes at subcellular domains during brain aging

在大脑衰老过程中,星形胶质细胞在亚细胞域表现出不同的 Ca2+ 变化

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作者:Fusheng Ding, Shanshan Liang, Ruijie Li, Zhiqi Yang, Yong He, Shaofan Yang, Qingtian Duan, Jianxiong Zhang, Jing Lyu, Zhenqiao Zhou, Mingzhu Huang, Haoyu Wang, Jin Li, Chuanyan Yang, Yuxia Wang, Mingyue Gong, Shangbin Chen, Hongbo Jia, Xiaowei Chen, Xiang Liao, Ling Fu, Kuan Zhang

Abstract

Astrocytic Ca2+ transients are essential for astrocyte integration into neural circuits. These Ca2+ transients are primarily sequestered in subcellular domains, including primary branches, branchlets and leaflets, and endfeet. In previous studies, it suggests that aging causes functional defects in astrocytes. Until now, it was unclear whether and how aging affects astrocytic Ca2+ transients at subcellular domains. In this study, we combined a genetically encoded Ca2+ sensor (GCaMP6f) and in vivo two-photon Ca2+ imaging to determine changes in Ca2+ transients within astrocytic subcellular domains during brain aging. We showed that aging increased Ca2+ transients in astrocytic primary branches, higher-order branchlets, and terminal leaflets. However, Ca2+ transients decreased within astrocytic endfeet during brain aging, which could be caused by the decreased expressions of Aquaporin-4 (AQP4). In addition, aging-induced changes of Ca2+ transient types were heterogeneous within astrocytic subcellular domains. These results demonstrate that the astrocytic Ca2+ transients within subcellular domains are affected by aging differently. This finding contributes to a better understanding of the physiological role of astrocytes in aging-induced neural circuit degeneration.

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