Surgery-induced downregulation of hippocampal sirtuin-1 contributes to cognitive dysfunction by inhibiting autophagy and activating apoptosis in aged mice

手术诱导的海马 sirtuin-1 下调通过抑制自噬和激活老年小鼠的细胞凋亡导致认知功能障碍

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作者:Qian-Juan Fang, Bing-Huan Chi, Qi-Cheng Lin, Chen-Miao Huang, Shao-Wu Jin, Jia-Jing Cai, Ke Nan, Yuan Han, Yuan-Xiang Tao, Hong Cao, Jun Li

Conclusion

These findings suggest that surgery-induced downregulation of hippocampal SIRT1 participates in cognitive impairment after surgery by inhibiting the autophagy process and activating apoptosis.

Methods

The aged (16-month-old) male C57BL/6 mice underwent anesthesia and surgery. Some mice received intraperitoneal injections of resveratrol, which is an activator of SIRT1, prior to exposure to splenectomy. To examine learning and memory behavior in different sets, the study performed a Morris water maze. Tissues from the hippocampus were harvested 1, 3 and 7 days after surgery. Western blotting and immunofluorescence analysis determined the expression of autophagy- and apoptosis- associated protein.

Results

This article demonstrated surgery but not anesthesia considerably affected memory behavior and downregulated SIRT1 expression in the aged mice. Interestingly, rescue of hippocampal SIRT1 expression ameliorated the cognitive impairment in the elderly mice under splenectomy. In addition, surgical trauma decreased Beclin-1 protein levels and the LC3-II/LC3-I ratio, while expression of p62, Bax and cleaved caspase-3 in hippocampal neurons increased. However, rescue of hippocampal SIRT1 expression considerably attenuated the surgery-induced downregulation of Beclin-1, increased the ratio of LC3-II/LC3-I, and decreased expression of p62, Bax, and cleaved caspase-3.

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