{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T03:50:40Z","timestamp":1765857040260,"version":"3.48.0"},"reference-count":65,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"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":["82171186"],"award-info":[{"award-number":["82171186"]}],"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":["82471278"],"award-info":[{"award-number":["82471278"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Lidocaine is widely used for perioperative pain management, but repeated exposure may cause neurotoxicity, including neurological deficits. This study investigates mechanisms underlying cognitive decline induced by repeated lidocaine exposure. Eighteen\u2010month\u2010old mice received repeated clinically relevant lidocaine infusions over 3\u2009days. Cognitive function was assessed by Morris water maze, Y\u2010maze and open field tests. Hippocampal pathology was examined via TEM, Nissl staining, immunofluorescence for astrocyte polarisation and A\u03b2 deposition, and western blot for tau, BDNF, TrkB, mTOR and autophagy proteins. The TrkB agonist 7,8\u2010DHF was used to modulate BDNF\/TrkB\/mTOR signalling. Repeated lidocaine exposure impaired cognition and induced Alzheimer's\u2010like hippocampal pathology, as evidenced by increased accumulation of A\u03b2 and tau toxic proteins, along with neuronal death. It reduced BDNF expression, inhibited TrkB phosphorylation, and activated mTOR signalling, leading to autophagy inhibition and pathological protein accumulation. Lidocaine shifted astrocytes towards the neurotoxic A1 phenotype, decreasing neuroprotective A2 astrocytes and BDNF synthesis. TrkB agonist treatment restored signalling, enhanced autophagy and improved cognitive deficits and pathology. Repeated lidocaine exposure promotes A1 astrocyte increase and A2 decrease, inhibiting autophagy via the BDNF\/TrkB\/mTOR pathway, resulting in toxic protein deposition and Alzheimer's\u2010like cognitive impairment.<\/jats:p>","DOI":"10.1111\/jcmm.70970","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T06:09:41Z","timestamp":1764482981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repeated Exposure to Lidocaine Induces Alzheimer's\u2010Like Cognitive Impairment and Neuropathology in Aged Mice Through BDNF\u2010Regulated Autophagy"],"prefix":"10.1111","volume":"29","author":[{"given":"Yongxin","family":"Huang","sequence":"first","affiliation":[{"name":"Shengli Clinical Medical College of Fujian Medical University, Department of Anesthesiology, Fujian Provincial Hospital Fuzhou University Affiliated Provincial Hospital  Fuzhou 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