{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:48:04Z","timestamp":1781326084989,"version":"3.54.1"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T00:00:00Z","timestamp":1693267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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>As a multi\u2010disease model, neuroinflammation, mitochondrial dysfunction, and oxidative stress might be involved in the pathogenic process of perioperative neurocognitive dysfunction (PND). Dynamin\u2010related protein 1 (Drp1) could mediate mitochondrial fission and play important roles in mitochondrial dynamic homeostasis and mitochondria function. The Drp1 may be involved in PND development. The cold\u2010inducible RNA\u2010binding protein (Cirbp) could bind to the 3\u2019\u2010UTR of the thioredoxin 1 (Trx1) mRNA, control oxidative stress, and improve mitochondrial function. In this study, we hypothesized that the Cirbp\u2010Trx1 pathway could ameliorate mitochondrial dysfunction and Drp1 levels in PND mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Differentially expressed genes were screened using the Gene Expression Omnibus (GEO) database GSE95426 and validated using PCR. Eighteen\u2010month\u2010old C57BL\/6 mice were subjected to tibial fracture surgery to generate a PND model. Cirbp was upregulated by hippocampal stereotaxic injections of over\u2010Cirbp plasmid according to the manufacturer's instructions for the in vivo DNA transfection reagent. Cirbp expression was measured using western blot (WB) and immunofluorescence (IF). The Morris water maze (MWM) was used to assess cognitive function. After behavioral testing, the hippocampal tissue was extracted to examine changes in mitochondrial Drp1, mitochondrial function, neuroinflammation, and oxidative stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Differential gene screening showed that Cirbp expression was significantly downregulated (fold change &gt;1.5, <jats:italic>p<\/jats:italic>\u2009=\u20090.003272) in the PND model. In this study, we also found that Cirbp protein levels were downregulated, accompanied by an impairment of cognition, a decrease in superoxide dismutase (SOD) activity, and an increase in malondialdehyde (MDA) content, mitochondrial Drp1 levels, neuroinflammation, and apoptosis. Cirbp overexpression increased Trx1 protein levels and reversed the damage. However, this protective effect was abolished by PX\u201012 treatment with a Trx1 inhibitor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The Cirbp\u2010Trx1 pathway may regulate mitochondrial dysfunction and mitochondrial Drp1 expression in the hippocampus of PND mice to ameliorate cognitive dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14433","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T08:20:32Z","timestamp":1693297232000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The cold\u2010inducible <scp>RNA<\/scp>\u2010binding protein\u2014Thioredoxin 1 pathway ameliorates mitochondrial dysfunction and mitochondrial dynamin\u2010related protein 1 level in the hippocampus of aged mice with perioperative neurocognitive dysfunction"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7774-6618","authenticated-orcid":false,"given":"Jingyao","family":"Huang","sequence":"first","affiliation":[{"name":"Laboratory of Anesthesia and Critical Care Medicine in Colleges and Universities of Shandong Province, School of Anesthesiology Weifang Medical University  Weifang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Anesthesia and Critical Care Medicine in Colleges and Universities of Shandong Province, School of Anesthesiology Weifang Medical University  Weifang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Anesthesia and Critical Care Medicine in Colleges and Universities of Shandong Province, School of Anesthesiology Weifang Medical University  Weifang 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