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

Abstract

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.

Fine processes of Nestin-GFP–positive radial glia-like stem cells in the adult dentate gyrus ensheathe local synapses and vasculature

“…Studies of physical exercise have shown that increases in neurogenesis with running (92) are coupled to increases in angiogenesis (93), and these factors are associated with an increase in cognitive function (94). Angiogenesis occurs alongside neurogenesis in embryonic development when the BBB is formed, but the BBB does not fully mature until 3 weeks postnatally, when cues from the neuroepithelium are thought to drive the wrapping of vessels by astrocytes (95).…”

BDNF-stimulated intracellular signalling mechanisms underlie exercise-induced improvement in spatial memory in the male Wistar rat

“…This is in agreement with other studies that have reported cellular proliferation in the dentate gyrus of rats with exercise that is both forced and of short duration (less than three weeks [43,44]). Cell proliferation has been shown to increase after as little as three days of voluntary exercise in mice, becoming statistically significant only after 10 days [45]. However, there is some evidence that the stages of neurogenesis occur at a different rate in rats than in mice [46].…”

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

“…The process of angiogenesis is believed to contribute to hippocampal neurogenesis to some degree; indeed the Gage laboratory observed dense clusters of proliferating cells in close association with the vasculature (Palmer et al, 2000). Treadmill exercise and voluntary wheel running have been reported to increase blood vessel density, numbers of glucose transporter (Glut-1) + blood vessels and cerebral blood volume in animal models (Black et al, 1990;Pereira et al, 2007;Van der Borght et al, 2009). It is noteworthy that Pereira et al (2007) correlated the exercise-induced increases in DG cerebral blood volume with postmortem measurements of cell survival.…”