Article

Journal of Huazhong University of Science and Technology [Medical Sciences]

, Volume 33, Issue 4, pp 530-535

Role of GSK-3β in isoflurane-induced neuroinflammation and cognitive dysfunction in aged rats

  • Shi-yong Li李世勇Affiliated withDepartment of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • , Xin Chen陈 欣Affiliated withDepartment of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • , Ye-ling Chen陈晔凌Affiliated withDepartment of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • , Lei Tan谭 蕾Affiliated withDepartment of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • , Yi-lin Zhao赵以林Affiliated withDepartment of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • , Jin-tao Wang王金韬Affiliated withDepartment of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • , Qiang Xiang向 强Affiliated withDepartment of Anesthesiology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • , Ai-lin Luo罗爱林Affiliated withDepartment of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Email author 

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Summary

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.

Key words

isoflurane GSK-3β cognitive dysfunction neuroinflammation