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

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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.

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Authors and Affiliations

  1. Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Shi-yong Li  (李世勇), Xin Chen  (陈 欣), Ye-ling Chen  (陈晔凌), Lei Tan  (谭 蕾), Yi-lin Zhao  (赵以林), Jin-tao Wang  (王金韬) & Ai-lin Luo  (罗爱林)

  2. Department of Anesthesiology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China

    Qiang Xiang  (向 强)

Authors
  1. Shi-yong Li  (李世勇)
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  2. Xin Chen  (陈 欣)
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  3. Ye-ling Chen  (陈晔凌)
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  4. Lei Tan  (谭 蕾)
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  5. Yi-lin Zhao  (赵以林)
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  6. Jin-tao Wang  (王金韬)
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  7. Qiang Xiang  (向 强)
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  8. Ai-lin Luo  (罗爱林)
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Corresponding author

Correspondence to Ai-lin Luo  (罗爱林).

Additional information

This work was supported by grants from the National Natural Science Foundation of China (No. 81271233, No. 81200880, No. 31240030).

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Li, Sy., Chen, X., Chen, Yl. et al. Role of GSK-3β in isoflurane-induced neuroinflammation and cognitive dysfunction in aged rats. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 33, 530–535 (2013). https://doi.org/10.1007/s11596-013-1154-3

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  • DOI: https://doi.org/10.1007/s11596-013-1154-3

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