Physical exercise-triggered adiponectin increase mitigates impairment of hippocampal neurogenesis and behavioral despairs in a corticosterone-induced stress model
Ang LiSuk-yu YauRuby L.C.HooKenneth K.Y.ChengAimin XuKwok-fai So
Department of Medicine,Li Ka Shing Faculty of Medicine,the University of Hong KongDepartment of Anatomy,Li Ka Shing Faculty of Medicine,the University of Hong KongDivision of Medical Sciences,University of Victoria,British Columbia,CanadaState Key Laboratory of Pharmaceutical Biotechnology,Li Ka Shing Faculty of Medicine,the University of Hong KongResearch Centre of Heart,Brain,Hormone and Healthy Ageing,Li Ka Shing Faculty of Medicine,the University of Hong KongDepartment of Pharmacology and Pharmacy,Li Ka Shing Faculty of Medicine,the University of Hong KongDepartment of Ophthalmology,Li Ka Shing Faculty of Medicine,the University of Hong KongState Key Laboratory of Brain and Cognitive Science,Li Ka Shing Faculty of Medicine,the University of Hong KongGuangdong-Hong Kong-Macau Institute of CNS Regeneration,Jinan UniversityGuangdong Key Laboratory of Brain Function and Diseases,Jinan University
摘要：A growing body of evidence suggests that suppression of neurogenesis at the mood-regulatory regions in adulthood might be a key biological alteration relating psychological depression. Physical exercise has proven to enhance neuron production in the hippocampal dentate gyrus, subsequently exerting anti-depressant-like effects by an unknown mechanism. The adipocyte-secreted molecule adiponectin that is permeable to the blood-brain barrier and resembles physical exercise in regulating metabolism has recently been found neuroprotective. Accordingly, we examined whether adiponectin potentially participated in the running-elicited promotion of hippocampal neurogenesis and mitigation of depression in a mouse model of stress. The data showed that in adult male mice, daily injections of corticosterone managed to induce behavioral despairs comparably in both adiponectin-knockout（KO） and wild-type（WT） strains, as evidenced by the significant elevation of circulating corticosterone levels, atrophy of adrenal glands, prolonged immobile durations in the tail suspension and forced swimming tests, and lowered preference to sucrose. Concurrently, the numbers of newborn, proliferating and immature neuronal cells in the dentate gyrus were all reduced, indicating an inhibited hippocampal neurogenesis. Running alleviated these phenotypes in WT but not in KO runners. Likewise, it raised the hippocampal adiponectin levels only in WT mice, which remained undetected in KO animals. In contrast, BDNF and IGF-1 presumably dominating this process were comparable among all groups. Proliferation of cultured neural progenitor cells was decelerated by corticosterone, which could be reversed with adiponectin addition. However, differential signaling pathways might be involved, because the AMPK pathway blocker dorsomorphin diminished adiponectin’s rescue, while corticosterone alone did not affectthe phosphorylation of AMPK. Taken together, hippocampal adiponectin increase following running might restore the corticosterone-elicited suppression of hippocampal neurogenesis through activating the AMPK pathway, ultimately lowering depressive severity. Our finding unveils a novel way in counteracting stress-evoked depression with adiponectin by adopting strategies like physical exercise, and the same method might be applied elsewhere to neuropsychological disorders caused by compromised hippocampal neurogenesis.