Effect Of Aerobic Exercise On Depression In Rats: Role Of Mitophagy

Abstract

: Depression is a common health problem and a major cause of agrypnia and disability. Recent evidence supports an anti-depressive effect of aerobic exercise on unpredictable chronic mild stress (UCMS)-induced depression in rats; however, the biological mechanism remains to be investigated. PURPOSE: To investigate whether aerobic exercise could improve UCMS-induced depression and alter mitophagy in depressive rats. METHOD: Thirty-six male Sprague-Dawley rats were randomly divided into three groups: a control group (Con, n=12), a UCMS-induced depression group (UCMS, n=12), and a UCMS-induced depression plus aerobic exercise group (UCMS+E, n=12). After 4 weeks of UCMS stimulation, rats in the UCMS+E group carried out 3 weeks (60 min/day) of swimming exercise. A sucrose preference test (SPT) was performed, and the content of 5-hydroxytryptamine (5-HT) was measured to verify whether the depression model was successful. A Morris water maze (MWM) test was used to evaluate spatial learning and memory ability. The expression levels of mitophagy-related proteins (Beclin1, LC3-I, LC3-II and P62) were determined by Western blot. Statistically significant group differences were assessed by using one-way ANOVAs and post-hoc tests. RESULTS: Based on the change of sucrose consumption and the expression level of 5-HT following UCMS treatment, the depression model was successfully established in the rats. Spatial learning and memory ability were lower in the UCMS group than the Con group (both p<0.05), but improved in the UCMS+E group (both p<0.05). According to the Western blot results, the expression levels of Beclin1 (Con: 0.37±0.02, UCMS: 0.26±0.04, UCMS+E: 0.43±0.07) and P62 (Con: 0.34±0.03, UCMS: 0.20±0.02, UCMS+E: 0.31±0.05), as well as the LC3-II/LC3-I ratio (Con: 0.36±0.05, UCMS: 0.19±0.04, UCMS+E: 0.33±0.04) were significantly lower in the UCMS group than the Con group (all p<0.05), but were significantly higher in the UCMS+E group than the UCMS group (all p<0.05). CONCLUSION: This study suggests that rats with UCMS-induced depression presented alterations in mitophagy. Three weeks of aerobic exercise significantly up-regulated mitophagy in depressive rats. Therefore, mitophagy may play an important role in the biological mechanism underlying the anti-depressive effect of aerobic exercise.