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

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

doi:10.3389/fnagi.2022.1029533

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

Front Aging Neurosci. 2022 Oct 28:14:1029533. doi: 10.3389/fnagi.2022.1029533. eCollection 2022.

Authors

Fusheng Ding^{1

2

3}, Shanshan Liang³, Ruijie Li^{3

4}, Zhiqi Yang³, Yong He³, Shaofan Yang³, Qingtian Duan³, Jianxiong Zhang³, Jing Lyu⁵, Zhenqiao Zhou⁵, Mingzhu Huang³, Haoyu Wang³, Jin Li³, Chuanyan Yang³, Yuxia Wang³, Mingyue Gong³, Shangbin Chen^{1

2}, Hongbo Jia^{4

5

6}, Xiaowei Chen^{3

7}, Xiang Liao⁸, Ling Fu^{1

2}, Kuan Zhang³

Affiliations

¹ Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China.
² MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, China.
³ Brain Research Center and State Key Laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University, Chongqing, China.
⁴ Advanced Institute for Brain and Intelligence and School of Physical Science and Technology, Guangxi University, Nanning, China.
⁵ Brain Research Instrument Innovation Center, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China.
⁶ Combinatorial NeuroImaging Core Facility, Leibniz Institute for Neurobiology, Magdeburg, Germany.
⁷ Guangyang Bay Laboratory, Chongqing Institute for Brain and Intelligence, Chongqing, China.
⁸ Center for Neurointelligence, School of Medicine, Chongqing University, Chongqing, China.

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.

Keywords: Ca2+ transients; aging; astrocyte; branches; branchlets and leaflets; endfeet.