2. Academic Validation
  3. Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice

Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice

  • Nat Commun. 2024 Jan 10;15(1):449. doi: 10.1038/s41467-024-44704-6.
Danyang Chen # 1,  Qianqian Lou # 1,  Xiang-Jie Song # 1,  Fang Kang 1,  An Liu 2,  Changjian Zheng 3,  Yanhua Li 1,  Di Wang 1,  Sen Qun 4,  Zhi Zhang 5 6,  Peng Cao 7,  Yan Jin 8
Affiliations

Affiliations

  • 1 Department of Anesthesiology, the First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.
  • 2 Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230022, China.
  • 3 Department of Anesthesiology, the First Affiliated Hospital of Wannan Medical College, Wuhu, 241002, China.
  • 4 Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.
  • 5 Department of Anesthesiology, the First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China. zhizhang@ustc.edu.cn.
  • 6 The Center for Advanced Interdisciplinary Science and Biomedicine, Institute of Health and Medicine, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China. zhizhang@ustc.edu.cn.
  • 7 Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China. pengcao@ustc.edu.cn.
  • 8 Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China. jinyan@ustc.edu.cn.
  • # Contributed equally.
PMID: 38200023 DOI: 10.1038/s41467-024-44704-6
Abstract

Anxiety-associated symptoms following acute stress usually become extinct gradually within a period of time. However, the mechanisms underlying how individuals cope with stress to achieve the extinction of anxiety are not clear. Here we show that acute restraint stress causes an increase in the activity of GABAergic neurons in the CeA (GABACeA) in male mice, resulting in anxiety-like behaviors within 12 hours; meanwhile, elevated GABACeA neuronal CX3CL1 secretion via MST4 (mammalian sterile-20-like kinase 4)-NF-κB-CX3CL1 signaling consequently activates microglia in the CeA. Activated microglia in turn inhibit GABACeA neuronal activity via the engulfment of their dendritic spines, ultimately leading to the extinction of anxiety-like behaviors induced by restraint stress. These findings reveal a dynamic molecular and cellular mechanism in which microglia drive a negative feedback to inhibit GABACeA neuronal activity, thus facilitating maintenance of brain homeostasis in response to acute stress.

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