Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-44704-6 |
| _version_ | 1797355679241994240 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Danyang Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T14:14:35Z |
| format | Article |
| id | doaj.art-d901cbb97df648a9aa86079758c50c99 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T14:14:35Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-d901cbb97df648a9aa86079758c50c992024-01-14T12:29:32ZengNature PortfolioNature Communications2041-17232024-01-0115111510.1038/s41467-024-44704-6Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male miceDanyang Chen0Qianqian Lou1Xiang-Jie Song2Fang Kang3An Liu4Changjian Zheng5Yanhua Li6Di Wang7Sen Qun8Zhi Zhang9Peng Cao10Yan Jin11Department 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 ChinaDepartment 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 ChinaDepartment 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 ChinaDepartment 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 ChinaDepartment of Physiology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Anesthesiology, the First Affiliated Hospital of Wannan Medical CollegeDepartment 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 ChinaDepartment 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 ChinaStroke Center and Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment 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 ChinaStroke Center and Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaStroke Center and Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaAbstract 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.https://doi.org/10.1038/s41467-024-44704-6 |
| spellingShingle | 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 Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice Nature Communications |
| title | Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice |
| title_full | Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice |
| title_fullStr | Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice |
| title_full_unstemmed | Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice |
| title_short | Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice |
| title_sort | microglia govern the extinction of acute stress induced anxiety like behaviors in male mice |
| url | https://doi.org/10.1038/s41467-024-44704-6 |
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