We found that CUMS induced depressive-like behaviors including decreased sucrose preference ratio, prolonged immobility and reduced locomotor and exploratory activity; cognitive deficits including spatial learning and memory impairment; reduced dendritic spine density and number of branches; thinned postsynaptic density; downregulated SIRT1/microRNA-134 pathway, decreased BDNF and synaptic proteins including synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) expression in the hippocampus.