Astrocyte Ezrin defines resilience to stress-induced depressive behaviours in mice

Astrocyte atrophy is the main histopathological hallmark of major depressive disorder (MDD) in humans and in animal models of depression. Here we demonstrated that manipulating Ezrin expression specifically in astrocytes significantly increases the resilience of mice to chronic unpredictable mild stress (CUMS). Overexpression of Ezrin in astrocytes from the medial prefrontal cortex (mPFC) rescued depressive-like behaviours induced by CUMS, whereas down-regulation of Ezrin in astrocytes from the mPFC increased mouse susceptibility to CUMS and promoted depressive-like behaviours. These behavioural changes correlated with astrocytic morphology. Astrocytes from the mPFC of mice sensitive to CUMS demonstrated significant atrophy; similar atrophy was found in astrocytes from animals with down-regulated Ezrin expression. On the contrary, morphology of astrocytes remained unchanged in animals resistant to CUMS and in animals with astrocytic overexpression of Ezrin. Morphological changes also correlated with Ezrin immunoreactivity, which was low in mice with depressive-like behaviours and high in mice resistant to stress. We conclude that Ezrin-dependent morphological remodelling of astrocytes defines the sensitivity of mice to stress; high Ezrin expression renders them stress resilient, whereas low Ezrin expression promotes depressive-like behaviour in response to chronic stress.

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Publication Details

Journal
National Science Review
Published
2025-11-03
DOI
https://doi.org/10.1093/nsr/nwaf480
Citations
1
Primary Topic
Nerve injury and regeneration
Type
article
Field-Weighted Citation Impact
0.91

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article

Astrocyte Ezrin defines resilience to stress-induced depressive behaviours in mice

Baoman Li, Bin Zhou, Péter Illés, Si-Le Liu et al.
1 citations
National Science Review
Nerve injury and regeneration
0.91
article

Astrocyte Ezrin defines resilience to stress-induced depressive behaviours in mice

Baoman Li, Bin Zhou, Péter Illés, Si-Le Liu, Alexey Semyanov, Chenju Yi, Si-Si Lin, Binjie Chen, Jing Guo, Yong Tang, Alexei Verkhratsky, Jianqin Niu, Ruotian Jiang, J Tong, Xing-Ying Ren
article en
1 citations

Abstract

Astrocyte atrophy is the main histopathological hallmark of major depressive disorder (MDD) in humans and in animal models of depression. Here we demonstrated that manipulating Ezrin expression specifically in astrocytes significantly increases the resilience of mice to chronic unpredictable mild stress (CUMS). Overexpression of Ezrin in astrocytes from the medial prefrontal cortex (mPFC) rescued depressive-like behaviours induced by CUMS, whereas down-regulation of Ezrin in astrocytes from the mPFC increased mouse susceptibility to CUMS and promoted depressive-like behaviours. These behavioural changes correlated with astrocytic morphology. Astrocytes from the mPFC of mice sensitive to CUMS demonstrated significant atrophy; similar atrophy was found in astrocytes from animals with down-regulated Ezrin expression. On the contrary, morphology of astrocytes remained unchanged in animals resistant to CUMS and in animals with astrocytic overexpression of Ezrin. Morphological changes also correlated with Ezrin immunoreactivity, which was low in mice with depressive-like behaviours and high in mice resistant to stress. We conclude that Ezrin-dependent morphological remodelling of astrocytes defines the sensitivity of mice to stress; high Ezrin expression renders them stress resilient, whereas low Ezrin expression promotes depressive-like behaviour in response to chronic stress.

National Science ReviewVol. 13(2)
Army Medical University (CN), Sun Yat-sen University (CN), Sichuan University (CN), University of Manchester (GB), West China Hospital of Sichuan University (CN), Jiaxing University (CN), The Seventh Affiliated Hospital of Sun Yat-sen University (CN), Science and Technology Department of Sichuan Province (CN), Institute of Forensic Science (CN), Institute of Pharmacology (CZ), Second Affiliated Hospital of Chengdu University of Traditional Chinese (CN), Chengdu University of Traditional Chinese Medicine (CN), China Medical University (CN), Leipzig University (DE)
National Natural Science Foundation of China, Eusko Jaurlaritza, Javna Agencija za Raziskovalno Dejavnost RS, Ministerio de Ciencia e Innovación, Russian Science Foundation, China Medical University, Sichuan Provincial Administration of Traditional Chinese Medicine, Sanming Project of Medicine in Shenzhen, Science and Technology Planning Project of Guangdong Province
Openalex Percentile: Top 20%
Nerve injury and regeneration
0.91
DOIOpen Access PDFOpenAlex
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