Physical exercise leads to rapid adaptations in hippocampal vasculature: temporal dynamics and relationship to cell proliferation and neurogenesis

Hippocampus. 2009 Oct;19(10):928-36. doi: 10.1002/hipo.20545.


Increased levels of angiogenesis and neurogenesis possibly mediate the beneficial effects of physical activity on hippocampal plasticity. This study was designed to investigate the temporal dynamics of exercise-induced changes in hippocampal angiogenesis and cell proliferation. Mice were housed with a running wheel for 1, 3, or 10 days. Analysis of glucose transporter Glut1-positive vessel density showed a significant increase after 3 days of wheel running. Cell proliferation in the dentate gyrus showed a trend towards an increase after 3 days of running and was significantly elevated after 10 days of physical exercise. Ten days of wheel running resulted in a near-significant increase in the number of immature neurons, as determined by a doublecortin (DCX) staining. In the second part of the study, the persistence of the exercise-induced changes in angiogenesis and cell proliferation was determined. The running wheel was removed from the cage after 10 days of physical activity. Glut-1 positive vessel density and hippocampal cell proliferation were determined 1 and 6 days after removal of the wheel. Both parameters had returned to baseline 24 h after cessation of physical activity. The near-significant increase in the number of DCX-positive immature neurons persisted for at least 6 days, indicating that new neurons formed during the period of increased physical activity had survived. Together these experiments show that the hippocampus displays a remarkable angiogenic and neurogenic plasticity and rapidly responds to changes in physical activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / blood supply
  • CA1 Region, Hippocampal / physiology
  • Cell Count
  • Cell Proliferation*
  • Dentate Gyrus / blood supply
  • Dentate Gyrus / physiology
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Glucose Transporter Type 1 / metabolism
  • Hippocampus / blood supply*
  • Hippocampus / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism
  • Microvessels / physiology
  • Neovascularization, Physiologic / physiology*
  • Neurogenesis / physiology*
  • Neurons / physiology
  • Neuropeptides / metabolism
  • Physical Conditioning, Animal / physiology*
  • Running / physiology
  • Time Factors


  • Dcx protein, mouse
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Glucose Transporter Type 1
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Slc2a1 protein, mouse