{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T20:05:31Z","timestamp":1789329931070,"version":"build-2803163510"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301717"],"award-info":[{"award-number":["82301717"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M730077"],"award-info":[{"award-number":["2023M730077"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515110205"],"award-info":[{"award-number":["2022A1515110205"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515011957"],"award-info":[{"award-number":["2023A1515011957"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Microglia, as resident macrophages in the brain, play an important role in depression. Heat shock protein 60 (HSP60), as a chaperone protein, plays a role in cell stress. However, the role of microglial HSP60 in depression remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CX3CR1\u2010CreER was used to generate microglial\u2010specific HSP60 knockout (HSP60 cKO) mice. Behavioral tests, western blotting, Golgi staining, biochemical assays, and proteomics were employed to assess depression\u2010like symptoms, microglial activation, and synaptic changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HSP60 cKO male mice exhibited depressive\u2010like behaviors, without anxiety\u2010like behavior, including increased immobility in the forced swimming and tail suspension tests, reduced sucrose preference, and elevated corticosterone (CORT) levels, indicating HPA axis activation. Microglial activation was confirmed by the increased expression levels of CD68 and CD86, the elevated transcription of the\n                      <jats:italic>cybb<\/jats:italic>\n                      gene, and reduced branch complexity. Enhanced phagocytosis of excitatory synapses, reduced dendritic spine density, and decreased glutamate levels were observed, with downregulation of synaptic proteins (AMPAR2, Synapsin\u20101, PSD95), indicating dysregulated synaptic pruning. Moreover, GO analysis showed 20 significant differentially expressed proteins (DEPs) from proteomics are associated with the presynaptic endosome, which plays a crucial role in maintaining synaptic function. Treatment with PLX3397, a CSF1R inhibitor, alleviated depressive\u2010like behaviors and restored synaptic density in HSP60 cKO male mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HSP60 deletion in microglia leads to overactivation of microglia, impaired synaptic function, and depression\u2010like behaviors, highlighting the importance of microglial homeostasis in mood regulation and the potential therapeutic role of microglial modulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70394","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T07:41:21Z","timestamp":1744789281000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Depletion of\n                    <scp>HSP60<\/scp>\n                    in Microglia Leads to Synaptic Dysfunction and Depression\u2010Like Behaviors Through Enhanced Synaptic Pruning in Male Mice"],"prefix":"10.1111","volume":"31","author":[{"given":"Wenhui","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single\u2010Cell and Extracellular Vesicles, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences Dali University  Dali China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liusuyan","family":"Tian","sequence":"additional","affiliation":[{"name":"The Seventh Affiliated Hospital Sun Yat\u2010Sen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyan","family":"Yang","sequence":"additional","affiliation":[{"name":"The Seventh Affiliated Hospital Sun Yat\u2010Sen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9396-8528","authenticated-orcid":false,"given":"Weifen","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shenzhen University Medical School Shenzhen University  Shenzhen China"},{"name":"State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology Peking University Shenzhen Graduate School  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-clinpsy-072220-021440"},{"issue":"5","key":"e_1_2_11_3_1","first-page":"562","article-title":"Anxiety, Depression, and Stress in Response to the Coronavirus Disease\u201019 Pandemic","volume":"88","author":"P\u00e9rez\u2010Cano H. 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