Swimming Exercise Pretreatment Attenuates Postoperative Delirium-Like Behavior in Type 2 Diabetic Rats by Enhancing Mitochondrial Biogenesis Through Activation of SIRT2 Deacetylation

Abstract

Postoperative delirium (POD) is a common postsurgical complication that seriously affects patients' prognosis and imposes a heavy burden on families and society. Type 2 diabetes mellitus (T2DM) is a major risk factor for POD. The susceptibility mechanisms of POD in T2DM individuals and the role of exercise preconditioning remain unclear. Adult rats with and without T2DM were used to assess the promotive effect of diabetes on postoperative delirium-like behavior. The diabetic rats were also subjected to a swimming exercise program before surgery. The potential beneficial effect of exercise preconditioning on postoperative cognition was evaluated by examining neurobehavior, hippocampal neuroinflammation, mitochondrial morphology, and function in diabetic rats. Finally, underlying mechanisms were further analyzed by exploring the role of the sirtuin family in vivo and in vitro. We found that performing tibial fracture surgery resulted in delirium-like behavior and inhibited hippocampal mitochondrial biogenesis in diabetic rats but not in healthy rats. Preoperative swimming exercise was beneficial in attenuating delirium-like behavior, inhibiting neuroinflammation, and improving mitochondrial biogenesis and function. Preoperative swimming exercise achieved these positive effects by upregulating SIRT2-mediated peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) deacetylation and activating mitochondrial biogenesis in T2DM rats.