Adiponectin, a cytokine secreted by mature adipocytes, proves to be neuroprotective. We have previously reported that running triggers adiponectin up-regulation which subsequently promotes generation of hippocampal neurons and thereby alleviates depression-like behaviors in non-stressed mice. However, under the stressing condition, whether adiponectin could still exert antidepressant-like effects following exercise remained unexplored. In this study, by means of repeated corticosterone injections to mimic stress insult and voluntary wheel running as physical exercise intervention, we examined whether exercise-elicited antidepressive effects might involve adiponectin’s regulation on hippocampal neurogenesis and dendritic plasticity in stressed mice. Here we show that repeated injections of corticosterone inhibited hippocampal neurogenesis and impaired dendritic morphology of neurons in the dentate gyrus of both wild-type and adiponectin-knockout mice comparably, which subsequently evoked depression-like behaviors. 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 proliferation of neural progenitors and dendritic morphology of neurons in the hippocampal dentate gyrus, which may depend on activation of the AMPK pathway.

脂联素是成熟脂肪细胞分泌的一种细胞因子，被证明具有神经保护作用。我们以前曾报道过跑步会触发脂联素上调，继而促进海马神经元的生成，从而减轻无压力小鼠的抑郁样行为。然而，在压力条件下，运动后脂联素是否仍能发挥抗抑郁样作用尚待探讨。在这项研究中，通过反复注射皮质酮以模拟压力损伤和自愿轮转作为体育锻炼干预手段，我们检查了运动引起的抗抑郁作用是否可能涉及脂联素对应激小鼠海马神经发生和树突可塑性的调节。在这里，我们表明，反复注射皮质酮可抑制野生型和脂联素敲除小鼠的齿状回中的海马神经发生和受损的神经元树突形态，这随后引起了抑郁样行为。自愿性轮转减弱了皮质类固醇抑制的神经发生并增强了海马体的树突可塑性，最终减少了野生型小鼠（而非脂联素敲除小鼠）的抑郁样行为。我们进一步证明，这种促神经生成作用的作用可能是通过激活AMP依赖性激酶（AMPK）途径实现的。