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

• Published in: Journal of neuroinflammation Vol. 18; no. 1; pp. 41 - 16
• Main Authors: Liu, Qiang, Sun, Yi-Man, Huang, Hui, Chen, Chen, Wan, Jie, Ma, Lin-Hui, Sun, Yin-Ying, Miao, Hui-Hui, Wu, Yu-Qing
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04.02.2021; BioMed Central; BMC
• Subjects: Anesthesia; Animal cognition; Antibodies; Brain research; Calcium; Care and treatment; Cognition disorders; Cognitive ability; Complications; Enzyme-linked immunosorbent assay; Enzymes; Fractures; Health aspects; Hippocampus; Hippocampus (Brain); Immunofluorescence; Inflammation; Interleukin 6; Laboratory animals; Life span; Long-term potentiation; Malondialdehyde; Memory; Microglia; Mitochondria; Mitochondrial oxidative stress; Morbidity; NAD; Nervous system diseases; Neurodegenerative diseases; Neuroinflammation; Oxidative stress; Postoperative cognitive dysfunction; Prevention; Proteins; SIRT3; Superoxide dismutase; Surgery; Synaptic plasticity; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Western blotting; China; United States > US; Mitochondrial oxidative stress; Neuroinflammation; Postoperative cognitive dysfunction; Synaptic plasticity; Microglia; SIRT3
• DOI: 10.1186/s12974-021-02089-z
• ISSN: 1742-2094

Postoperative 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. SIRT3 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. Overexpression 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. The 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.