Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin

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 t...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2014-11, Vol.111 (44), p.15810-15815
Main Authors: Yau, Suk Yu, Li, Ang, Hoo, Ruby L. C., Ching, Yick Pang, Christie, Brian R., Lee, Tatia M. C., Xu, Aimin, So, Kwok-Fai
Format: Article
Language:English
Subjects:
Adipocytes - metabolism
Adipocytes - pathology
Adiponectin - agonists
Adiponectin - metabolism
AMP-Activated Protein Kinases - metabolism
Animals
Antidepressants
Antidepressive Agents - therapeutic use
Biological Sciences
Brain
Cell growth
Cell Line, Tumor
Cell Proliferation
Depression - drug therapy
Depression - metabolism
Exercise
Genotypes
Hippocampus
Hippocampus - metabolism
Hippocampus - pathology
Insulin
Mental depression
Mental health care
Mice
Neurogenesis
Neurons
Phosphorylation
Physical Conditioning, Animal
Receptors
Receptors, Adiponectin - metabolism
Rodents
Running
Signal Transduction
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Summary: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, exerciseinduced 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1415219111