Increased Oxidative Damage Contributes to Mitochondrial Dysfunction in Muscle of Depressed Rats Induced by Chronic Mild Stress Probably Mediated by SIRT3 Pathway

Depressed individuals are at an increased risk of developing age-related physiological diseases. Moreover, although it has been shown to be closely linked to skeletal muscle disease, the underlying mechanism is not well understood. In this study, we further investigated the pathophysiology and possible mechanism in the muscle tissue of depressed rats. The model of depression was developed by chronic mild stress (CMS) for seven weeks as indicated by reduced sucrose preference and a shorter total travelled distance, fewer grid line crossings, less time in the center zone in the open field test than that of controls. In addition, depressed rats exhibited declined physiological activity characterized by reduced locomotor activity and thermogenesis. Moreover, CMS altered the levels of 5-hydroxytryptophan (5-HT), Neuropeptide Y (NPY), and corticosterone (CORT) in serum and hippocampus. What’s more, impaired mitochondrial ultrastructure and function as shown by transmission electron microscope and reduced mitochrondrial DNA (mtDNA) integrity, ATP production, which was associated with increased cellular ROS and decreased superoxide dismutase activity in muscle tissue of CMS-induced depressed rats. Overall, our present study provides a new perspective for depressed individuals accompanied by fatigue and new ideas for future treatment of depression complications.