{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:55:19Z","timestamp":1788965719434,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T00:00:00Z","timestamp":1651449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Inhibition of histone deacetylase (HDAC) may be a useful approach in the treatment of disorders characterized by cognitive dysfunction. Dexmedetomidine (DEX), an \u03b12\u2010adrenoceptor (\u03b12\u2010AR) agonist, has demonstrated neuroprotective effects. Here, we attempted to investigate the protective effects of DEX on postoperative cognitive dysfunction (POCD) involving HDAC2. Male C57BL\/6 mice were selected to develop a POCD model, where HDAC2, HIF\u20101\u03b1, and PFKFB3 expression was quantified. DEX was administered before POCD modeling. Then the cognitive function of POCD mice was evaluated with the open field and Y\u2010maze tests. Meanwhile, lipopolysaccharide (LPS) was employed to induce BV\u20102 microglial cells to simulate the inflammatory response. The contents of TNF\u2010\u03b1, IL\u20106, and IL\u201010 were measured by enzyme\u2010linked immunosorbent assay (ELISA) in mouse serum and BV\u20102 cell supernatant. Abundant expression of HDAC2, HIF\u20101\u03b1, and PFKFB3 was confirmed in POCD mice (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Cognitive dysfunction in POCD mice could be alleviated following pharmacological inhibition of HDAC2 by FK228 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Mechanistically, HDAC2 upregulated HIF\u20101\u03b1 and PFKFB3 and promoted the secretion of inflammatory factors in LPS\u2010exposed BV\u20102 cells (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). DEX attenuated neuroinflammation and the resulting cognitive dysfunction by decreasing HDAC2 expression and HIF\u20101\u03b1\u2010dependent PFKFB3 upregulation in POCD mice (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In conclusion, DEX\u2010regulated HDAC2 may play an inhibitory role in mice with POCD through regulation of the HIF\u20101\u03b1\/PFKFB3 axis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jbt.23044","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T13:03:54Z","timestamp":1651496634000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Effects of dexmedetomidine on cognitive dysfunction and neuroinflammation via the HDAC2\/HIF\u20101\u03b1\/PFKFB3 axis in a murine model of postoperative cognitive dysfunction"],"prefix":"10.1002","volume":"36","author":[{"given":"Yu\u2010Fang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology 904th Hospital of The Joint Logistics Support Force of the PLA  Wuxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology 904th Hospital of The Joint Logistics Support Force of the PLA  Wuxi P. R. China"},{"name":"School of Anesthesiology Xuzhou Medical University  Xuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long\u2010Fei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology 904th Hospital of The Joint Logistics Support Force of the PLA  Wuxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology 904th Hospital of The Joint Logistics Support Force of the PLA  Wuxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Feng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology 904th Hospital of The Joint Logistics Support Force of the PLA  Wuxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7819-922X","authenticated-orcid":false,"given":"Xing\u2010Zhi","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology 904th Hospital of The Joint Logistics Support Force of the PLA  Wuxi P. R. 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