{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:58:04Z","timestamp":1781528284256,"version":"3.54.1"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2025GXNSFBA069259"],"award-info":[{"award-number":["2025GXNSFBA069259"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2025GXNSFBA069470"],"award-info":[{"award-number":["2025GXNSFBA069470"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Depression is a significant global health issue characterized by complex underlying mechanisms. This study aimed to investigate the role of cholinergic neuron\u2010specific heat shock protein 60 (HSP60) in modulating lipopolysaccharide (LPS)\u2010induced neuroinflammation and depressive\u2010like behaviours in mice.<\/jats:p>\n                    <jats:p>Cholinergic neuron\u2010specific HSP60 knockout mice were generated by crossing Hsp60\u2010flox mice with Chat\u2010cre mice. Genotyping confirmed the successful creation of the knockout. The effects of LPS on weight loss, behavioural changes, cytokine levels, neuroinflammation markers and signalling pathway proteins were assessed. Behavioural assessments included the tail suspension test and sucrose preference test.<\/jats:p>\n                    <jats:p>HSP60 knockout mice exhibited mitigated weight loss in response to LPS. Behavioural tests indicated that HSP60 deficiency alleviated LPS\u2010mediated depressive\u2010like behaviours without affecting locomotor activity. In the hippocampus, LPS treatment significantly altered cytokine levels, increasing pro\u2010inflammatory cytokines at the same time as decreasing anti\u2010inflammatory cytokines. HSP60 knockout mice partially reversed these effects, showing increased anti\u2010inflammatory and decreased pro\u2010inflammatory cytokines. LPS\u2010induced upregulation of neuroinflammation markers such as glial fibrillary acidic protein, NLRP3 (i.e. NOD\u2010, LRR\u2010 and pyrin domain\u2010containing protein 3) and p\u2010IKK\u03b1\/\u03b2 [i.e. the phosphorylated forms of the catalytic subunits of the I\u03baB kinase (IKK) complex, specifically\u00a0IKK\u03b1\u00a0(CHUK) and\u00a0IKK\u03b2] was significantly reduced in HSP60 knockout mice. Additionally, LPS\u2010induced elevation of phosphorylated eukaryotic translation initiation factor 2\u03b1 levels in the hippocampus was attenuated by HSP60 deficiency, without affecting other signalling pathway proteins.<\/jats:p>\n                    <jats:p>\n                      These findings suggest that HSP60 in cholinergic neurons plays a critical role in regulating LPS\u2010induced neuroinflammation and depressive\u2010like behaviours. Targeting HSP60 in cholinergic neurons may provide a therapeutic approach for mitigating neuroinflammation and associated depressive symptoms.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70564-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Specific knockout of HSP60 in cholinergic neurons could protect against LPS\u2010induced physiological and behavioral impairments, including mitigated weight loss, improved depressive\u2010like behaviors, and unaffected locomotor activity.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Cholinergic neuron\u2010specific HSP60 deletion could attenuate neuroinflammation by reversing LPS\u2010induced cytokine imbalance, suppressing key inflammatory markers (GFAP, NLRP3, cGAS, p\u2010IKK\u03b1\/\u03b2), and crucially, by preserving hippocampal acetylcholine levels, a key neurotransmitter with established anti\u2010inflammatory properties.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>HSP60 deficiency selectively reduces the LPS\u2010induced phosphorylation of the eukaryotic translation initiation factor 2\u03b1 (p\u2010eIF2\u03b1) in the hippocampus, indicating a targeted modulation of the cellular stress and protein synthesis regulation pathway, without altering other major signaling molecules.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp290049","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T01:04:47Z","timestamp":1778202287000},"page":"4910-4925","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The deletion of HSP60 in cholinergic neurons alleviates LPS\u2010induced depressive\u2010like behaviours in mice by reducing neuroinflammation"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9019-7320","authenticated-orcid":false,"given":"Xiangzan","family":"Wei","sequence":"first","affiliation":[{"name":"Key Laboratory of Biological Molecular Medicine Research Guangxi Medical University, Education Department of Guangxi Zhuang Autonomous Region  Nanning Guangxi China"},{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences, Guangxi Medical University  Nanning Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoni","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Pathology Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Ouyang","sequence":"additional","affiliation":[{"name":"School of Urban Governance and Public Affairs Suzhou City University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine the First Affiliated Hospital of Guangzhou University of Chinese 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