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We investigated the prophylactic effects of liraglutide, a GLP-1 analog, on delirium-like behaviors in aged mice undergoing cardiac surgery and explored the underlying mechanisms focusing on neuroinflammation, mitochondrial dysfunction, and synaptic plasticity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Using a cardiac ischemia-reperfusion animal model to mimic cardiac surgery, we assessed delirium-like behaviors, microglial activation, NLRP3 inflammasome activation, mitophagy, synaptic engulfment, and synaptic plasticity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Cardiac surgery triggered delirium-like behaviors, concomitant with heightened microglial and NLRP3 inflammasome activation and impaired mitochondrial function and synaptic plasticity. Pretreatment with liraglutide ameliorated these adverse outcomes. Mechanistically, liraglutide enhanced mitophagy, thereby inhibiting NLRP3 inflammasome activation and subsequent microglial activation. Furthermore, liraglutide counteracted surgery-induced synaptic loss and impairment of synaptic plasticity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Liraglutide exerts protective effects against delirium-like behaviors in aged mice post-cardiac surgery, potentially through bolstering microglia mitophagy, curtailing neuroinflammation, and preserving synaptic integrity. This highlights the potential of liraglutide as a promising perioperative strategy for delirium prevention in cardiac surgery patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00213-023-06492-7","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T02:01:36Z","timestamp":1700100096000},"page":"687-698","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Liraglutide ameliorates delirium-like behaviors of aged mice undergoing cardiac surgery by mitigating microglia activation via promoting mitophagy"],"prefix":"10.1007","volume":"241","author":[{"given":"Min","family":"Jia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Chun","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-xue","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-jun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"key":"6492_CR1","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.ebiom.2018.10.021","volume":"37","author":"A Alam","year":"2018","unstructured":"Alam A, Hana Z, Jin Z, Suen KC, Ma D (2018) Surgery, neuroinflammation and cognitive impairment. 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