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Evidence showed that HMGB1 signaling might be regulated by Connexin (Cx) 36 in inflammatory diseases of central nervous system (CNS). Our study aimed to further explore the role of Cx36 in depressive\u2010like behaviors and its relationship with HMGB1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>After 4\u2010week chronic stress, behavioral tests were conducted to evaluate depressive\u2010like behaviors, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and open field test (OFT). Western blot analysis and immunofluorescence staining were used to observe the expression and location of Cx36. Enzyme\u2010linked immunosorbent assay (ELISA) was adopted to detect the concentrations of inflammatory cytokines. And the excitability and inward currents of hippocampal neurons were recorded by whole\u2010cell patch clamping.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The expression of Cx36 was significantly increased in hippocampal neurons of mice exposed to CUMS, while treatment with glycyrrhizinic acid (GZA) or quinine could both down\u2010regulate Cx36 and alleviate depressive\u2010like behaviors. The proinflammatory cytokines like HMGB1, tumor necrosis factor alpha (TNF\u2010\u03b1), and interleukin\u20101\u03b2 (IL\u20101\u03b2) were all elevated by CUMS, and application of GZA and quinine could decrease them. In addition, the enhanced excitability and inward currents of hippocampal neurons induced by lipopolysaccharide (LPS) could be reduced by either GZA or quinine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Inhibition of Cx36 in hippocampal neurons might attenuates HMGB1\u2010mediated depressive\u2010like behaviors induced by CUMS through down\u2010regulation of the proinflammatory cytokines and reduction of the excitability and intracellular ion overload.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.2470","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T09:04:45Z","timestamp":1643360685000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Inhibition of Connexin 36 attenuates HMGB1\u2010mediated depressive\u2010like behaviors induced by chronic unpredictable mild stress"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5499-4368","authenticated-orcid":false,"given":"Qian","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Psychiatry Faculty of Psychology Second Military Medical University  Shanghai P. 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