{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:55:13Z","timestamp":1792000513105,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,3]],"date-time":"2024-03-03T00:00:00Z","timestamp":1709424000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011790","name":"Xiangya Hospital, Central South University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011790","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>Patients with sepsis\u2010associated encephalopathy (SAE) often exhibit cognitive impairments. Despite this, the underlying mechanisms of SAE remain largely unexplored. Here, we explored the role of serotonergic neurotransmission in cognitive dysfunction of two mouse models of SAE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The mouse models of SAE were established by injection of lipopolysaccharide (LPS, 10\u2009mg\/kg, intraperitoneal) and cecal ligation puncture (CLP) respectively. Barnes maze, new object recognition test and open field test were used to evaluate the effects of fluoxetine (selective serotonin reuptake inhibitor) and cyproheptadine (nonselective 5\u2010HT<jats:sub>2<\/jats:sub> receptor antagonist) on cognition and motor activity of mice. Additionally, WAY100635 (5\u2010HT<jats:sub>1A<\/jats:sub> receptor antagonist) was co\u2010administered with fluoxetine to explore the mechanism underlying effect of fluoxetine on cognitive impairments of SAE. Enzyme\u2010linked immunosorbent assay (ELISA) was performed to determine 5\u2010HT levels in hippocampus, brainstem and frontal lobe of experimental groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both LPS\u2010induced sepsis and CLP induced sepsis resulted in a notable learning deficit. Fluoxetine ameliorated, while cyproheptadine aggravated, cognitive impairment in two classic mouse models of SAE. The cognition\u2010enhancing effect of fluoxetine is reversed by WAY100635. Decreased 5\u2010HT levels in hippocampus, brainstem and frontal lobe were observed in LPS septic model and CLP septic model. Notably, both fluoxetine and cyproheptadine significantly increased 5\u2010HT levels in those brain regions in LPS septic model. Additionally, fluoxetine significantly increased 5\u2010HT levels in frontal lobe of CLP septic model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study demonstrated that serotonergic neurotransmission plays a significant role in mechanisms underlying cognitive impairment in SAE. These findings contribute to identification of novel targets to prevent and arrest cognitive impairment in SAE.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14655","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T02:28:45Z","timestamp":1709519325000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Serotonergic neurotransmission mediated cognitive dysfunction in two mouse models of sepsis\u2010associated encephalopathy"],"prefix":"10.1111","volume":"30","author":[{"given":"Chen","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fafa","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingchen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University  Changsha China"},{"name":"Bioinformatics Center &amp; 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