Adiponectin mediates beneficial effects of running on depression-like behaviors and hippocampal neurogenesis
Suk-Yu Yau1Ang Li2Ruby L.C.Hoo2,3,4Yick-Pang Ching3,5Brian R.Christie1Tatia M.C.Lee6,7,8Aimin Xu2,4,9Kwok-Fai So3,5,6,10,11,12
1. Division of Medical Sciences,University of Victoria,3800 Finnerty Road,Victoria,BC,Canada V8P 5C22. Departments of Medicine,Li Ka Shing Faculty of Medicine,University of Hong Kong3. Research Centre of Heart,Brain,Hormone and Healthy Ageing,Li Ka Shing Faculty of Medicine,University of Hong Kong4. State Key Laboratory of Pharmaceutical Biotechnology,Li Ka Shing Faculty of Medicine,University of Hong Kong5. Department of Anatomy,Li Ka Shing Faculty of Medicine,University of Hong Kong6. State Key Laboratory of Brain and Cognitive Science,Li Ka Shing Faculty of Medicine,University of Hong Kong7. Laboratories of Neuropsychology,University of Hong Kong8. Cognitive Affective Neuroscience,University of Hong Kong9. Departmentof Pharmacology and Pharmacy,Li Ka Shing Faculty of Medicine,University of Hong Kong10. Departmenrt of Ophthalmology,Li Ka Shing Faculty of Medicine,University of Hong Kong11. Guangdong-Hong Kong-Macau Institute of CNS Regeneration,Jinan University12. Guangdong Key Laboratory of Brain Function and Diseases,Jinan University
摘要：Adiponectin is an adipocyte-secreted protein exhibiting insulin-sensitizing, anti-diabetic, anti-inflammatory and anti-atherogenic properties. Here we investigated whether exercise-elicited antidepressant effects are potentially mediated by adiponectin through its regulation on hippocampal neurogenesis. ADN deficient and wildtype mice were subjected to wheel running for 14 days. Immunostaining for bromodeoxyuridine, doublecortin and Ki67 were used to examine changes in hippocampal cell proliferation and differentiation. Depressive phenotypes of the mice were examined using forced swim test, tail suspension test and sucrose preference test. Hippocampal progenitor cell culture and neuroblastoma cell line were used to examine the related downstream pathways. Adiponectin could entry into the brain from blood stream. Increasing its levels in the brain resembled running in increasing cell proliferation and decreasing depressive-like behaviors. Adiponectin deficiency diminished exercise-increased hippocampal neurogenesis and-reduced depression-like behaviors. In vitro analyses indicated that adiponectin increased cell proliferation in both hippocampal progenitor cells and N2 a cells. The neurogenic effects of adiponectin were mediated by the adiponectin receptor 1（ADNR1）, as siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of adiponectin to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression.