Increased Oxidative Damage Contributes to Mitochondrial Dysfunction in Muscle of Depressed Rats Induced by Chronic Mild Stress Probably Mediated by SIRT3 Pathway
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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.
Keywords:depression oxidative damage SIRT3 signaling pathway mitochondrial dysfunction skeletal muscle
The authors express their gratitude to Prof. Qishan Wang (School of Agriculture and Biology, Department of Animal Sciences, Shanghai Jiao Tong University) for his/her help in revising our article for data analysis.
This work was supported by a grant from the National Natural Science Foundation of China (no. 31701028).
COMPLIANCE WITH ETHICAL STANDARDS
Conflict of interests. All authors agree with the presented findings, have contributed to the work and declare no conflict of interest.
Statement on the welfare of animals. Animals were treated in accordance with Guide for the Care and Use of Laboratory Animals (8th edition, National Academies Press), and all the experiments were carried out in accordance with the Guiding Principles for the Use of Animals in Zhejiang University of Technology, Hangzhou, China.
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