AIM:To explore the molecular mechanism by which treadmill exercise reshapes the homeostasis of mitochondrial dynamics and alleviates depression-like behavior.METHODS:The mouse model of depression-like be-havior was established by electronic foot shock plus restraint stress.The depression-like mice were intervened with tread-mill exercise.The neurobehavior of mice was evaluated using the open field test and elevated plus-maze test,neuronal in-jury was detected by Nissl staining and TUNEL,and the expression of mitochondrial dynamics-related proteins was detect-ed by Western blot and immunofluorescence.RESULTS:Five weeks of electronic foot shock plus restraint stress success-fully established the depression-like mouse model,and neurobehavioral tests showed that the mice exhibited depression-like behaviors.In depression-like mice,neuronal synapses were degraded and neuronal apoptosis increased,while tread-mill exercise reduced neuronal damage and alleviated abnormal neurobehavior in depression-like mice.The mechanism study shows that the expression of mitochondrial fission-related protein 1(Fis1)and dynamin-related protein 1(Drp1)in-volved in mitochondrial division is up-regulated,and the expression of mitofusin 2(MFN2)and optic atrophy 1 protein(OPA1)involved in mitochondrial fusion is down-regulated in the cerebral cortex of depression-like mice.Notably,tread-mill exercise reverses the expression of these mitochondrial dynamics-related proteins and reshapes the homeostasis of mi-tochondrial dynamics.CONCLUSION:Mitochondrial dynamics disorder is involved in the pathological process of neu-robehavioral changes in mice with depression-like behavior.Treadmill exercise reshapes the homeostasis of mitochondrial dynamics and alleviates depression-like behavior.This study provides a scientific reference for the clinical application of exercise therapy as an adjuvant therapy in the intervention of diseases associated with depression-like behavior.

AIM:To explore the molecular mechanism by which treadmill exercise reshapes the homeostasis of mitochondrial dynamics and alleviates depression-like behavior.METHODS:The mouse model of depression-like be-havior was established by electronic foot shock plus restraint stress.The depression-like mice were intervened with tread-mill exercise.The neurobehavior of mice was evaluated using the open field test and elevated plus-maze test,neuronal in-jury was detected by Nissl staining and TUNEL,and the expression of mitochondrial dynamics-related proteins was detect-ed by Western blot and immunofluorescence.RESULTS:Five weeks of electronic foot shock plus restraint stress success-fully established the depression-like mouse model,and neurobehavioral tests showed that the mice exhibited depression-like behaviors.In depression-like mice,neuronal synapses were degraded and neuronal apoptosis increased,while tread-mill exercise reduced neuronal damage and alleviated abnormal neurobehavior in depression-like mice.The mechanism study shows that the expression of mitochondrial fission-related protein 1(Fis1)and dynamin-related protein 1(Drp1)in-volved in mitochondrial division is up-regulated,and the expression of mitofusin 2(MFN2)and optic atrophy 1 protein(OPA1)involved in mitochondrial fusion is down-regulated in the cerebral cortex of depression-like mice.Notably,tread-mill exercise reverses the expression of these mitochondrial dynamics-related proteins and reshapes the homeostasis of mi-tochondrial dynamics.CONCLUSION:Mitochondrial dynamics disorder is involved in the pathological process of neu-robehavioral changes in mice with depression-like behavior.Treadmill exercise reshapes the homeostasis of mitochondrial dynamics and alleviates depression-like behavior.This study provides a scientific reference for the clinical application of exercise therapy as an adjuvant therapy in the intervention of diseases associated with depression-like behavior.