Qiang Liu1, Yi-Man Sun1, Hui Huang1, Chen Chen1, Jie Wan1, Lin-Hui Ma1, Yin-Ying Sun1, Hui-Hui Miao2, Yu-Qing Wu3. 1. Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Tongshan Road 209, Xuzhou, 221004, P.R. China. 2. Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, P.R. China. iverymhh@hotmail.com. 3. Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Tongshan Road 209, Xuzhou, 221004, P.R. China. xzmcyqwu@163.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. METHODS: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. RESULTS: 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. CONCLUSION: 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.
Authors: Jacob Steinmetz; Karl Bang Christensen; Thomas Lund; Nicolai Lohse; Lars S Rasmussen Journal: Anesthesiology Date: 2009-03 Impact factor: 7.892
Authors: Patrick Miller-Rhodes; Cuicui Kong; Gurpreet S Baht; Priyanka Saminathan; Ramona M Rodriguiz; William C Wetsel; Harris A Gelbard; Niccolò Terrando Journal: J Neuroinflammation Date: 2019-10-28 Impact factor: 8.322