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Hippocampal neuroinflammation and impairment of the normal structure and function of microglia are closely associated with depression. To investigate the effects of LXRs agonist (GW3965) on neuroinflammation and microglia in the hippocampal formation of mice with chronic unpredictable stress (CUS)\u2010induced depression, depressive\u2010like behaviors were evaluated by behavioral tests, hippocampal LXRs gene expression were evaluated by qRT\u2010PCR, the protein expression levels of interleukin\u20101\u03b2, tumor necrosis factor\u2010\u03b1, inducible nitric oxide synthase, nuclear factor kappa B, and cluster of differentiation 206 were estimated by western blotting, modern stereological methods were used to precisely quantify the total number of microglia in each hippocampal subregion, and immunofluorescence was used to detect the density of activated microglia and the morphology of microglia. We found that GW3965 alleviated the depressive\u2010like behavior induced by CUS, reversed the decrease in hippocampal LXR\u03b1 and LXR\u03b2 induced by CUS, increased the protein expression of pro\u2010inflammatory factors, and decreased the protein expression of antiinflammatory factors induced by CUS. Moreover, CUS intervention significantly increased the number of microglia in the CA1 region, CA2\/3 region, and dentate gyrus and the density of activated microglia in the CA2\/3 region and dentate gyrus and significantly decreased the endpoints of microglial branches and process length of microglia in the dentate gyrus, while 4\u00a0weeks of injections with GW3965 reversed these changes. These findings suggest that regulating the number, activated state, and morphology of microglia in hippocampal subregions might be an important basis for the antidepressant effects of LXRs.<\/jats:p>","DOI":"10.1002\/cne.25380","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T06:43:42Z","timestamp":1656312222000},"page":"2852-2867","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The liver X receptors agonist GW3965 attenuates depressive\u2010like behaviors and suppresses microglial activation and neuroinflammation in hippocampal subregions in a mouse depression model"],"prefix":"10.1002","volume":"530","author":[{"given":"Jing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Basic Medicine Chongqing Medical University  Chongqing China"},{"name":"Laboratory of Stem Cells and Tissue Engineering, College of Basic Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Tissue Engineering, College of Basic Medicine Chongqing Medical University  Chongqing China"},{"name":"Department of Histology and Embryology, College of Basic Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Tissue Engineering, College of Basic Medicine Chongqing Medical University  Chongqing China"},{"name":"Department of Histology and Embryology, College of Basic Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Xiao","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Tissue Engineering, College of Basic Medicine Chongqing Medical University  Chongqing China"},{"name":"Department of Histology and Embryology, College of Basic Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Tang","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Tissue Engineering, College of Basic Medicine Chongqing Medical University  Chongqing China"},{"name":"Department of Histology and Embryology, College of Basic Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liang","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Tissue Engineering, College of Basic Medicine Chongqing Medical University  Chongqing China"},{"name":"Department of Pathophysiology, College of Basic Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Basic Medicine Chongqing Medical University  Chongqing China"},{"name":"Laboratory of Stem Cells and Tissue Engineering, College of Basic Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Tissue Engineering, College of Basic Medicine Chongqing Medical University  Chongqing China"},{"name":"Department of Histology and Embryology, College of Basic Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Deng","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Tissue Engineering, College of Basic Medicine Chongqing Medical University  Chongqing China"},{"name":"Department of Histology and Embryology, College of Basic Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Lab Teaching &amp; 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