title: Role of GSK-3β in isoflurane-induced neuroinflammation and cognitive dysfunction in aged rats.
abstract: This study investigated the role of glycogen synthase kinase-3β (GSK-3β) in isoflurane-induced neuroinflammation and cognitive dysfunction in aged rats. The hippocampi were dissected from aged rats which had been intraperitoneally administered lithium chloride (LiCl, 100 mg/kg) and then exposed to 1.4% isoflurane for 6 h. The expression of GSK-3β was detected by Western blotting. The mRNA and protein expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Morris water maze was employed to detect spatial memory ability of rats. The results revealed that the level of GSK-3β was upregulated after isofurane exposure. Real-time PCR analysis demonstrated that isoflurane anesthesia increased mRNA levels of TNF-α, IL-1β and IL-6, which was consistent with the ELISA results. However, these changes were reversed by prophylactic LiCl, a non-selective inhibitor of GSK-3β. Additionally, we discovered that LiCl alleviated isoflurane-induced cognitive impairment in aged rats. Furthermore, the role of GSK-3β in isoflurae-induced neuroinflammation and cognitive dysfunction was associated with acetylation of NF-κB p65 (Lys310). In conclusion, these results suggested that GSK-3β is associated with isoflurane-induced upregulation of proinflammatory cytokines and cognitive disorder in aged rats.
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Shi-Yong
authors.initials: SY
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ye-Ling
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jin-Tao
authors.initials: JT
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiang
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. ailinluo@hotmail.com.
authors.forename: Ai-Lin
authors.initials: AL
authors.lastname: Luo
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D007530:Isoflurane / Q000009:adverse effects*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007530:Isoflurane; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3
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