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

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  • Danyang Chen

    (University of Science and Technology of China)

  • Qianqian Lou

    (University of Science and Technology of China)

  • Xiang-Jie Song

    (University of Science and Technology of China)

  • Fang Kang

    (University of Science and Technology of China)

  • An Liu

    (Anhui Medical University)

  • Changjian Zheng

    (the First Affiliated Hospital of Wannan Medical College)

  • Yanhua Li

    (University of Science and Technology of China)

  • Di Wang

    (University of Science and Technology of China)

  • Sen Qun

    (University of Science and Technology of China)

  • Zhi Zhang

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Peng Cao

    (University of Science and Technology of China)

  • Yan Jin

    (University of Science and Technology of China)

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.

Suggested Citation

  • Danyang Chen & Qianqian Lou & Xiang-Jie Song & Fang Kang & An Liu & Changjian Zheng & Yanhua Li & Di Wang & Sen Qun & Zhi Zhang & Peng Cao & Yan Jin, 2024. "Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44704-6
    DOI: 10.1038/s41467-024-44704-6
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