Stress differentially regulates the effects of voluntary exercise on cell proliferation in the dentate gyrus of mice

Hippocampus. 2009 Oct;19(10):889-97. doi: 10.1002/hipo.20514.


It has been well-established that cell proliferation and neurogenesis in the adult mouse dentate gyrus (DG) can be regulated by voluntary exercise. Recent evidence has suggested that the effects of voluntary exercise can in turn be influenced by environmental factors that regulate the amount of stress an animal is exposed to. In this study, we use bromodeoxyuridine and proliferating cell nuclear antigen immunohistochemistry to show that voluntary exercise produces a significant increase in cell proliferation in the adult mouse DG in both isolated and socially housed mice. This effect on proliferation translates into an increase in neurogenesis and neuronal branching of new neurons in the mice that exercised. Although social condition did not regulate proliferation in young adult mice, an effect of social housing could be observed in mice exposed to acute restraint stress. Surprisingly, only exercising mice housed in isolated conditions showed an increase in cellular proliferation following restraint stress, whereas socially housed, exercising mice, failed to show a significant increase in proliferation. These findings indicate that social housing may increase the effects of any stressful episodes on hippocampal neurogenesis in the mouse DG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / physiology
  • Animals
  • Bromodeoxyuridine
  • Cell Proliferation*
  • Corticosterone / blood
  • Dentate Gyrus / cytology
  • Dentate Gyrus / physiopathology*
  • Housing, Animal
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism
  • Movement / physiology
  • Neurogenesis / physiology*
  • Neurons / cytology
  • Neurons / physiology*
  • Neuropeptides / metabolism
  • Physical Conditioning, Animal / physiology*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Restraint, Physical
  • Social Isolation
  • Stress, Psychological / blood
  • Stress, Psychological / physiopathology*
  • Volition


  • Microtubule-Associated Proteins
  • Neuropeptides
  • Proliferating Cell Nuclear Antigen
  • doublecortin protein
  • Bromodeoxyuridine
  • Corticosterone