• running wheel activity;
  • cerebrovascular system;
  • angiogenesis;
  • neurogenesis;
  • neuronal plasticity


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. © 2009 Wiley-Liss, Inc.