成都中医药大学Alexei Verkhratsky团队的最新研究提出了星形胶质细胞ezrin定义了小鼠对压力诱导的抑郁行为的恢复能力。这一研究成果于2025年11月4日发表在国际顶尖学术期刊《国家科学评论》上。

在这里，该研究组证明操纵ezrin在星形胶质细胞中的特异性表达可显著提高小鼠对慢性不可预测的轻度应激（CUMS）的恢复能力。前额叶皮层（PFC）星形胶质细胞中ezrin的过表达挽救了CUMS诱导的抑郁样行为，而PFC星形胶质细胞中ezrin的下调增加了小鼠对CUMS的易感性，并促进了抑郁样行为。这些行为变化与星形细胞形态相关。

CUMS敏感小鼠PFC星形胶质细胞明显萎缩；ezrin表达下调的动物的星形胶质细胞也出现了类似的萎缩。相反，在抗CUMS动物和ezrin过表达的动物中，星形胶质细胞的形态保持不变。形态学变化还与ezrin免疫反应性相关，在具有抑郁样行为的小鼠中，ezrin免疫反应性较低，而在抗应激小鼠中，ezrin免疫反应性较高。研究小组得出结论，星形胶质细胞依赖ezrin的形态重塑决定了小鼠对应激的敏感性：高ezrin表达使它们具有应激弹性，而低ezrin表达则促进慢性应激反应中的抑郁样行为。

据了解，星形胶质细胞萎缩是人类和抑郁症动物模型中重度抑郁症（MDD）的主要组织病理学标志。

附：英文原文

Title: Astrocyte ezrin defines resilience to stress-induced depressive behaviours in mice

Author: Lin, Si-Si, Zhou, Bin, Liu, Si-Le, Ren, Xing-Ying, Guo, Jing, Tong, Jing-Lin, Chen, Bin-Jie, Jiang, Ruo-Tian, Semyanov, Alexey, Yi, Chenju, Niu, Jianqin, Illes, Peter, Li, Baoman, Tang, Yong, Verkhratsky, Alexei

Issue&Volume: 2025-11-04

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 with ezrin expression specifically in astrocytes significantly increases the resilience of mice to chronic unpredictable mild stress (CUMS). Overexpression of ezrin in astrocytes from prefrontal cortex (PFC) rescued depressive-like behaviours induced by CUMS, whereas down-regulation of ezrin in astrocytes from PFC increased mice susceptibility to CUMS and promoted depressive-like behaviours. These behavioural changes correlated with astrocytic morphology. Astrocytes from PFC of mice sensitive to CUMS demonstrated significant atrophy; similar atrophy was found in astrocytes from animals with down-regulated ezrin expression. To the contrary morphology remains unchanged astrocytes 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.

DOI: 10.1093/nsr/nwaf480

Source:https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaf480/8314059?searchresult=1