{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T09:25:50Z","timestamp":1767086750264,"version":"3.48.0"},"reference-count":56,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471629"],"award-info":[{"award-number":["82471629"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301748"],"award-info":[{"award-number":["82301748"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515012129"],"award-info":[{"award-number":["2022A1515012129"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["SZSM202211010"],"award-info":[{"award-number":["SZSM202211010"]}],"id":[{"id":"10.13039\/501100012151","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":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is a global health event with progressive cognitive decline affecting millions of elderly people worldwide. Emerging evidence indicates that sevoflurane may be associated with AD progression. However, the underlying mechanism remains poorly understood. Herein, we explored the potential role of sevoflurane exposure in cognitive ability and the possible mechanisms of action in the early stage of Tg4510 (P301L tau) transgenic mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the novel object recognition test and Y\u2010maze test, we assessed the change in cognitive abilities in 3\u2010month\u2010old male WT mice and Tg4510 mice with or without 3% sevoflurane exposure. By histological analysis and western blot, we determined the effect of sevoflurane exposure on tau pathology, synaptic function, and neuroinflammatory response. TMT\u2010labeled proteomics technique coupled with bioinformatics analysis was performed to identify the potential key pathways or proteins involved in sevoflurane\u2010induced cognitive deterioration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Behavioral test showed that sevoflurane exposure exacerbated cognitive impairment of young Tg4510 mice. Pathologically, immunofluorescence demonstrated that sevoflurane exposure increased tau phosphorylation, synaptic defects, and neuroinflammatory response, which were further supported by the result of immunoblotting in Tg4510 mice exposed to sevoflurane. Proteomic analysis revealed an obvious decrease in autophagy\u2010related proteins including Sort1, Vps28, and Atg3 in the hippocampus of sevoflurane\u2010exposed Tg4510 mice compared to the nonexposed group. As an upstream signaling of autophagy, the AKT\/mTOR pathway was found to be inhibited in sevoflurane\u2010exposed Tg4510 mice. Moreover, our data also validated an inhibition of autophagy signaling associated with sevoflurane exposure in the context of tau pathology, as indicated by the upregulated expression of p62 and the downregulated expression of Sort1, Vps28, and Atg3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that autophagy signaling appears to be a promising target for intervention in sevoflurane\u2010induced cognitive impairment in the early tau pathology, which lays the foundation for further study of the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70694","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T15:30:54Z","timestamp":1765985454000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sevoflurane Exposure Exacerbates Memory Impairment and Pathological Manifestation by Inhibiting\n                    <scp>AKT<\/scp>\n                    \/m\n                    <scp>TOR<\/scp>\n                    \u2010Mediated Autophagy in\n                    <scp>P<\/scp>\n                    301\n                    <scp>L<\/scp>\n                    Tau Transgenic Mice"],"prefix":"10.1002","volume":"31","author":[{"given":"Kaiwu","family":"He","sequence":"first","affiliation":[{"name":"Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Department of Anesthesiology Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)  Shenzhen China"},{"name":"Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics Guangdong Medical University  Dongguan China"},{"name":"Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020\u20132024) Shenzhen Center for Disease Control and Prevention  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Affiliated Dongguan Hospital Southern Medical University (Dongguan People's Hospital)  Dongguan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youzhi","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Department of Anesthesiology Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)  Shenzhen 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