Role of GSK-3β in isoflurane-induced neuroinflammation and cognitive dysfunction in aged rats.
10.1007/s11596-013-1154-3
- Author:
Shi-yong LI
1
;
Xin CHEN
;
Ye-ling CHEN
;
Lei TAN
;
Yi-lin ZHAO
;
Jin-tao WANG
;
Qiang XIANG
;
Ai-lin LUO
Author Information
1. Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China, leeche@163.com.
- Publication Type:Journal Article
- MeSH:
Animals;
Cognition Disorders;
chemically induced;
metabolism;
pathology;
Glycogen Synthase Kinase 3;
metabolism;
Glycogen Synthase Kinase 3 beta;
Inflammation;
chemically induced;
metabolism;
pathology;
Isoflurane;
adverse effects;
Male;
Neurons;
drug effects;
metabolism;
pathology;
Rats;
Rats, Sprague-Dawley
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2013;33(4):530-535
- CountryChina
- Language:English
-
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.
