Sirtuin 3 (SIRT3) improves sevoflurane-induced postoperative cognitive impairment by regulating mitochondrial oxidative stress

SIRT3 mitigates sevoflurane-induced cognitive impairment

Authors

  • Changzong Dai Changsha First Hospital
  • Changquan Fu
  • Zhiguo Yi
  • Xiaohong Guan
  • Jiandong Deng

Keywords:

post-surgical cognitive impairment, Sevoflurane, Sirtuin 3 (SIRT3), Mitochondrial oxidative stress, Inflammatory response

Abstract

One of the most prevalent co-operative disorders is postoperative cognitive dysfunction (POCD), however, its pathogenesis remains unclear. Thus, the aim of this work was to evaluate SIRT3's impact on cognitive decline in aged mice under anesthesia. Adeno-associated virus SIRT3 vector (AAV-SIRT3) or empty vector (AAV-VEH) was injected into the hippocampal region of aged mice after sevoflurane induction in order to upregulate the expression of SIRT3. The expression levels of SIRT3, pro-inflammatory cytokines, and apoptotic factors in hippocampus tissues were identified by PCR, Western blotting, TUNEL staining, and enzyme-linked immunosorbent assay (ELISA), and the cognitive function of mice was assessed. The SIRT3 expression was down-regulated in the hippocampal tissue of anesthetized mice. SIRT3 overexpression can improve the learning and memory ability, reduce the escape latency, and increase the residence time in the platform and platform crossing ability of mice. The overexpression of SIRT3 in hippocampus can reduce the oxidative stress response and inflammatory response induced by anesthesia in mice, increase the superoxide dismutase (SOD) expression level, and decrease the expression level of MDA and inflammatory factors in hippocampus. In addition, SIRT3 overexpression can also reduce anesthetic-induced hippocampal cell apoptosis. By reducing the hippocampus mitochondrial oxidative stress response, SIRT3 plays a significant role in the pathophysiology of POCD in mice and is a potential target for POCD treatment and diagnosis.

Published

2024-02-28

Issue

Section

Original Research Articles