Abstract
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.
Highlights
The main symptoms of depression are lack of pleasure, fatigue, irritability and inattention, together with impairments in sleep, appetite and cognition, and even suicidal tendencies (Nestler et al, 2002)
Our results show that the prolonged COR injection comparably reduced hippocampal neurogenesis and impaired dendritic morphology of dentate gyrus (DG) neurons in wild-type C57BL/6J (WT) and ADN-KO mice, subsequently eliciting depressive behaviors
The further mechanistic investigation reveals that exerciseexerted enhancement of hippocampal neurogenesis under the stressing condition is potentially mediated through the ADN-AMP-dependent kinase (AMPK) pathway
Summary
The main symptoms of depression are lack of pleasure, fatigue, irritability and inattention, together with impairments in sleep, appetite and cognition, and even suicidal tendencies (Nestler et al, 2002). Two well-studied functional ADN receptors, AdipoR1 and AdipoR2, show distinct affinities to different oligomeric complexes: AdipoR1 has a high affinity to the globular form, while AdipoR2 has comparable affinities to both globular and full-length forms (Li et al, 2015). It has been demonstrated that ADN signaling participates in the regulation of numerous biological processes throughout the body, such as enhancing insulin sensitivity, modulating inflammation and energy expenditure (Lee and Kwak, 2014; Li et al, 2015), alleviating hypertensive vascular injury and protecting cardiovascular function (Guo et al, 2018), reducing oxidative stress and ameliorating renal endothelial dysfunction (Zha et al, 2017), promoting liver glucose and lipid metabolism (Holland et al, 2017), etc. Adiponectin can induce longterm chemical enhancement and promote presynaptic release probability (Pousti et al, 2018)
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