{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:46:53Z","timestamp":1792104413579,"version":"4.4.0"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"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":["81701052"],"award-info":[{"award-number":["81701052"]}],"id":[{"id":"10.13039\/501100001809","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":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Postoperative sleep disorder (PSD) and delirium, which may be associated with surgery and inhalational anesthetics, induce adverse effects in old adults. Emerging evidence indicates that circadian rhythm contributes to various neuropathological diseases, including Alzheimer's disease. Thus, we analyzed the potential role of circadian rhythm in PSD and delirium\u2010like behavior in aged mice and determined whether exogenous melatonin could facilitate entrainment of the circadian rhythm after laparotomy under sevoflurane anesthesia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We selected old C57BL\/6J mice which receiving laparotomy\/sevoflurane anesthesia as model animals. We employed buried food, open field, and Y maze test to assess delirium\u2010like behavior, and electroencephalography\/electromyography (EEG\/EMG) were used to investigate sleep changes. We analyzed the transcription rhythm of clock genes in superchiasmatic nucleus (SCN) to explore the effects of surgery and melatonin pretreatment on the circadian rhythm. Then, we measured melatonin receptor levels in SCN and ERK\/CREB pathway\u2010related proteins in hippocampus and prefrontal cortex to assess their role in PSDs and delirium\u2010like behavior.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Laparotomy under sevoflurane anesthesia had a greater influence than sevoflurane alone, leading to sleep disorder, a shift in sleep\u2013wake rhythm, and delirium\u2010like behavior. Bmal1, Clock, and Cry1 mRNA expression showed a peak shift, MT<jats:sub>1<\/jats:sub> melatonin receptor expression level was increased in the SCN, and p\u2010ERK\/ERK and p\u2010CREB\/CREB were decreased in hippocampus and prefrontal cortex of aged mice 1\u2009day after laparotomy. Melatonin showed significant efficacy in ameliorating PSD and delirium\u2010like behavior and restoring the circadian rhythm, reversing melatonin receptor and ERK\/CREB pathway expression abnormalities. In addition, most of the beneficial effect of melatonin was antagonized by luzindole, a melatonin receptor antagonist.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Melatonin receptors in SCN, circadian rhythm, and ERK\/CREB signaling pathway participate in the pathophysiological processes of PSD and delirium\u2010like behavior. Melatonin intervention could be a potential preventative approach for PSD and delirium.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14436","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T08:01:50Z","timestamp":1695369710000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Melatonin regulates the circadian rhythm to ameliorate postoperative sleep disorder and neurobehavioral abnormalities in aged mice"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6897-597X","authenticated-orcid":false,"given":"Xixi","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Peking University Third Hospital  Beijing 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