Exercise Improves Depressive Symptoms by Increasing the Number of Excitatory Synapses in the Hippocampus of CUS-Induced Depression Model Rats.

Exercise has been considered for the treatment of depression, but the mechanism by which exercise improves depression is still unclear. To clarify the mechanism, rats were randomly divided into the control, chronic unpredictable stress (CUS)/standard and CUS/running groups. The rats in the CUS/running group ran for four weeks. In this study, a sucrose preference test (SPT) was used to evaluate the depression-like symptoms in the rats, and western blot, immunohistochemical and stereological analyses were performed to study the expression of synaptic-related proteins in the hippocampus and the changes in excitatory synapses in each sub-region. The results show that sucrose preference in the CUS/standard group was significantly lower than that in the control group, but in the CUS/running group, sucrose preference was higher than that in the CUS/standard group. Surprisingly, there was no difference in the synaptic-related proteins in the hippocampus among groups. The CUS/standard group exhibited fewer spinophilin+ (Sp+) dendritic spines representing excitatory synapses in CA1, CA3 and dentate gyrus (DG) of the hippocampus than the control group, whereas the CUS/running group exhibited significantly more Sp+ dendritic spines in these regions than the CUS/standard group, indicating that excitatory synapses were reduced in depressed rats and that running exercises could reverse this change. We hypothesize that the changes in the number of excitatory synapses better reflect the changes in depressive symptoms than the level of synaptic proteins and that the effect of exercise on excitatory synapses in the sub-regions of the hippocampus may be an important structural indicator of the improvement of depressive symptoms.