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Voluntary wheel running attenuated corticosterone-suppressed neurogenesis and enhanced dendritic plasticity in the hippocampus, ultimately reducing depression-like behaviors in wild-type, but not adiponectin-knockout mice. We further demonstrate that such proneurogenic effects were potentially achieved through activation of the AMP-dependent kinase (AMPK) pathway. Our study provides the first evidence that adiponectin signaling is essential for physical exercise-triggered effects on stress-elicited depression by retaining the normal pro