How do physical exercise induce hippocampal neurogenesis and antidepressant effect? PNAS.2014.oct


Physical exercise is effective in treating  depression. There is some evidence to suggest that exercise increase certain brain functioning ( hippocampal dependent learning, hippocampal neurogenesis). A hormone secreted by adipocytes- adiponectin- is shown to mimic the metabolic effects of exercise. Both adiponectin and exercise exhibit antidiabetic, antiinflammatory, antiatherogenic and cardio-protective properties.

Adiponectin levels are low in depression. It increase with antidepressant treatments. Do adiponection  mediate the hippocampal neurogenesis due to exercise?

Suk Yu Yau et al report the results of their  animal study to address this interesting and important question in this article.

They compared the effects of exercise using knock out models. ( i.e. one group had their adiponectin gene removed). Exercise was given using running wheels. Behavioural tests include forced swim test and tail suspension test.Immunoassays and Western blot analysis of brain tissue was carried out.


1.Increased adiponection in CNS reduced depression like behaviours.

2. Adiponectin deficiency diminished the beneficial effects of exercise on depression like behaviours.

3. Adiponectin knock out diminished running induced hippocampal neurogenesis.

4. Adiponection stimulated hippocampal cell proliferation is mediated by adiponectin receptor 1


Knock down receptors model has limitations.


Exercise increase Adiponectin and this possibly  mediate the antidepressant effect via increasing neurogenesis. Adiponectin is a downstream mediator of the peroxisome proliferation-activated receptor-γ (PPARγ).  PPARy agonists as well as other agents  that can increase adinoceptin   could be useful antidepressants.

Summary of the article:

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormoneadiponectin.

Yau SY, Li A, Hoo RL, Ching YP, Christie BR, Lee TM, Xu A, So KF. Proc Natl Acad Sci U S A. 2014 Oct 20.

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