Role of GSK-3β in Isoflurane-induced Neuroinflammation and Cognitive Dysfunction in Aged Rats

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.