Exercise pattern and distance differentially affect hippocampal and cerebellar expression of FLK-1 and FLT-1 receptors in astrocytes and blood vessels

Aerobic exercise benefits the body and brain. In the brain, benefits include neuroprotection and improved cognition. These exercise-induced changes are attributed in part to angiogenesis: the growth of new capillaries from preexisting vessels. One critical factor involved in the regulation of angiogenesis is VEGF and its receptors Flk-1 and Flt-1. Although exercise is generally found to be beneficial, there are wide variations in exercise regimens across experiments. This study standardized some of these variations. Rats were assigned to a voluntary or a forced wheel running exercise condition. Within each condition, animals ran for either a long (1000 m) or short distance (500 m) for up to 24 h. Additionally, one voluntary group had unrestricted access to the wheels for the full 24 h. Exercising animals were then compared to inactive controls, based on unbiased stereological quantification of Flk-1 and Flt-1 immunohistochemical labeling in the hippocampus and cerebellum. Findings indicated that voluntary exercise, but not forced exercise, could significantly increase Flk-1 and Flt-1 expression in the hippocampus. Interestingly, Flk-1 expression was elevated in astrocytes and Flt-1 in vessels. In the cerebellum long distance forced exercise resulted in the least Flk-1 expression compared to other conditions, and Flt-1 expression in exercising animals either did not change or was suppressed relative to inactive controls.