Effects of exercise on activation of microglia and astrocytes and neuronal apoptosis in depressed rats

Du Juan; Zhang Yi; Hao Quanshui

doi:10.12307/2025.779

Abstract：BACKGROUND:Cyclooxygenase-2 can significantly enhance depressive-like behavior in rats,and cyclooxygenase-2 inhibitors have antidepressant effects.Exercise can significantly reduce depressive-like behaviors in depressed patients.However,it is currently unclear whether exercise exerts an antidepressant effect by inhibiting cyclooxygenase-2. OBJECTIVE:To reveal the effects of exercise on cyclooxygenase-2 expression,microglia and astrocyte activation,oxidative stress and neuronal apoptosis in depressed rats,as well as the possible molecular mechanisms. METHODS:The rat model of depression was induced by chronic unpredictable mild stimulation.After modeling,the chronic unpredictable mild stimulation rats were randomly divided into stimulation group and wheel running group,with 10 rats in each group.In addition,10 normal rats were selected as the control group.The rats in the control group and stimulation group did not exercise.The rats in the wheel running group performed forced wheel running for a total of 4 weeks.Depressive-like behavior was evaluated by sucrose preference test.Hippocampal cyclooxygenase-2 expression was detected by immunofluorescence staining.The expression of cyclooxygenase-2,Iba-1,CD11b,CD45,glial fibrillary acid protein,Bcl-2,Bax,and cleaved caspase-3 proteins in the hippocampus was detected by western blot analysis.The cyclooxygenase-2 mRNA level in the hippocampus was detected by RT-PCR.The activities of antioxidant enzymes in hippocampal tissue homogenates were determined using kits. RESULTS AND CONCLUSION:Compared with stimulation group,sucrose consumption was increased;cyclooxygenase-2 expression in hippocampus was decreased;superoxide dismutase,catalase,and glutathione peroxidase levels in hippocampus were increased;malonaldehyde level was decreased;Iba1,CD11b,and CD45 protein expression levels in hippocampus were decreased,and glial fibrillary acid protein level in hippocampus was decreased.Bcl-2 protein expression levels in the hippocampus were increased,while Bax and cleaved caspase-3 levels were decreased in wheel running group(P＜0.05).This study showed that wheel running could reduce depressive-like behavior by inhibiting the expression of cyclooxygenase-2 in the hippocampus of chronic unpredictable mild stimulation rats.In addition,wheel running can exert antidepressant effects by inhibiting microglia and astrocyte activation,oxidative stress,and neuronal apoptosis in the hippocampus.