title: Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin.
abstract: Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood-brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN 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, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression.
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Departments of Anatomy, Research Centre of Heart, Brain, Hormone and Healthy Ageing, Division of Medical Science, University of Victoria, BC, Canada V8P 5C2; and.
authors.forename: Suk Yu
authors.initials: SY
authors.lastname: Yau
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Departments of Anatomy, Medicine.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.affiliation: Research Centre of Heart, Brain, Hormone and Healthy Ageing, Medicine, State Key Laboratory of Pharmaceutical Biotechnology, Li Ka Shing Faculty of Medicine, Laboratories of.
authors.forename: Ruby L C
authors.initials: RL
authors.lastname: Hoo
authors.affiliation: Departments of Anatomy, Research Centre of Heart, Brain, Hormone and Healthy Ageing.
authors.forename: Yick Pang
authors.initials: YP
authors.lastname: Ching
authors.affiliation: Division of Medical Science, University of Victoria, BC, Canada V8P 5C2; and.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Christie
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Neuropsychology and Cognitive Affective Neuroscience, and Institute of Clinical Neuropsychology, The University of Hong Kong, Hong Kong SAR;
authors.forename: Tatia M C
authors.initials: TM
authors.lastname: Lee
authors.affiliation: Research Centre of Heart, Brain, Hormone and Healthy Ageing, Medicine, State Key Laboratory of Pharmaceutical Biotechnology, Li Ka Shing Faculty of Medicine, Laboratories of Pharmacology and Pharmacy, and amxu@hku.hk hrmaskf@hku.hk.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Departments of Anatomy, Research Centre of Heart, Brain, Hormone and Healthy Ageing, Ophthalmology, Guangdong-Hong Kong-Macau Institute of CNS Regeneration and Guangdong Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou 510632, China amxu@hku.hk hrmaskf@hku.hk.
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D052242:Adiponectin / Q000819:agonists / Q000378:metabolism*; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D055495:Neurogenesis; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D054419:Receptors, Adiponectin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D052242:Adiponectin; D000928:Antidepressive Agents; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse; D055372:AMP-Activated Protein Kinases
keywords: adiponectin; adiponectin receptor; depression-like behavior; hippocampal neurogenesis; physical exercise