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Dexmedetomidine (Dex) improves POCD, and we probed the effects of Dex on autophagy\u2013lysosomal pathway dysfunction in a POCD model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach<\/jats:title>\n                    <jats:p>A POCD mouse model was established and intraperitoneally injected with Dex. Cognitive function was evaluated by Morris water maze\/open field test\/novel object recognition assay. Levels of neurotransmitters\/inflammatory cytokines in hippocampus, and NLRP3\/ASC\/Cleaved Caspase\u20101 proteins were determined by ELISA\/Western blot. NLRP3 inflammasome\u2010mediated microglial activation\/astrocyte A1 differentiation in the hippocampal CA1 region were assessed by immunofluorescence assay. BV\u20102 cells were treated with lipopolysaccharide (LPS) and Dex and\/or the NLRP3 inflammasome activator Nigericin, and transfected with si\u2010TFEB for co\u2010culture with primary reactive astrocytes (RAs) to verify the function of Dex in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Dex alleviated cognitive dysfunction in POCD mice and repressed NLRP3 inflammasome\u2010mediated microglial activation and astrocyte A1 differentiation. NLRP3 inflammasome activation partially reversed the protective effect of Dex on the POCD condition. In vitro experiments verified the inhibitory properties of Dex on microglial activation and astrocyte A1 differentiation. Dex induces TFEB nuclear translocation, microglial autophagy and lysosomal biogenesis. By activating the autophagy\u2013lysosome pathway, Dex regulated NLRP3 inflammasome\u2010mediated microglial activation, inhibited astrocyte A1 differentiation and alleviated POCD in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and implications<\/jats:title>\n                    <jats:p>Dex regulates NLRP3 inflammasome\u2010mediated hippocampal microglial activation by promoting TFEB nuclear translocation and activating the autophagy\u2013lysosome pathway and inhibits astrocyte A1 differentiation, thereby alleviating POCD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.17378","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:25:53Z","timestamp":1736987153000},"page":"1683-1703","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Actions of dexmedetomidine in regulating NLRP3 in postoperative cognitive dysfunction in aged mice via the autophagy\u2013lysosome pathway"],"prefix":"10.1111","volume":"182","author":[{"given":"Zhi","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Neurobiology Xi'an Jiaotong University Health Science Center  Xi'an China"},{"name":"Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology, Xi'an Jiaotong University  Xi'an China"},{"name":"Department of Anesthesiology College of Stomatology, Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010na","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology, Xi'an Jiaotong University  Xi'an China"},{"name":"Department of Anesthesiology College of Stomatology, Xi'an Jiaotong University  Xi'an 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