Sirtuin 3 protects against anesthesia/surgery-induced cognitive decline in aged mice by suppressing hippocampal neuroinflammation

Journal of Neuroinflammation

Hui-Hui Miao¹  Lin-Hui Ma²  Yu-Qing Wu²  Qiang Liu²  Jie Wan²  Yi-Man Sun²  Hui Huang²  Chen Chen²  Yin-Ying Sun² 

[1] Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, 100050, Beijing, P.R. China;Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Tongshan Road 209, 221004, Xuzhou, P.R. China;

关键词: SIRT3;    Postoperative cognitive dysfunction;    Mitochondrial oxidative stress;    Neuroinflammation;    Microglia;    Synaptic plasticity;   

DOI  :  10.1186/s12974-021-02089-z

来源: Springer

【 摘 要 】

BackgroundPostoperative cognitive dysfunction (POCD) is a very common complication that might increase the morbidity and mortality of elderly patients after surgery. However, the mechanism of POCD remains largely unknown. The NAD-dependent deacetylase protein Sirtuin 3 (SIRT3) is located in the mitochondria and regulates mitochondrial function. SIRT3 is the only sirtuin that specifically plays a role in extending lifespan in humans and is associated with neurodegenerative diseases. Therefore, the aim of this study was to evaluate the effect of SIRT3 on anesthesia/surgery-induced cognitive impairment in aged mice.MethodsSIRT3 expression levels were decreased after surgery. For the interventional study, an adeno-associated virus (AAV)-SIRT3 vector or an empty vector was microinjected into hippocampal CA1 region before anesthesia/surgery. Western blotting, immunofluorescence staining, and enzyme-linked immune-sorbent assay (ELISA) were used to measure the oxidative stress response and downstream microglial activation and proinflammatory cytokines, and Golgi staining and long-term potentiation (LTP) recording were applied to evaluate synaptic plasticity.ResultsOverexpression of SIRT3 in the CA1 region attenuated anesthesia/surgery-induced learning and memory dysfunction as well as synaptic plasticity dysfunction and the oxidative stress response (superoxide dismutase [SOD] and malondialdehyde [MDA]) in aged mice with POCD. In addition, microglia activation (ionized calcium binding adapter molecule 1 [Iba1]) and neuroinflammatory cytokine levels (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-1β and IL-6) were regulated after anesthesia/surgery in a SIRT3-dependent manner.ConclusionThe results of the current study demonstrate that SIRT3 has a critical effect in the mechanism of POCD in aged mice by suppressing hippocampal neuroinflammation and reveal that SIRT3 may be a promising therapeutic and diagnostic target for POCD.

【 授权许可】

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