Date of Award

December 2016

Degree Type


Degree Name

Master of Science



First Advisor

Rodney A. Swain

Committee Members

Fred J. Helmstetter, Karyn M. Frick


Angiogenesis, Exercise, Flk-1, Flt-1, Vegf


Aerobic exercise benefits the body and brain. In the brain, these 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 the exercise regimens used across experiments. This study standardized some of these variations. In this study, rats were either assigned to a voluntary wheel running or a forced wheel running exercise condition. Within each condition, animals ran at either a high (1,000 wheel revolutions) or low (500 wheel revolutions) intensity for up to 24 hours. Animals were removed from the running wheels when they reached their respective revolutions. In addition, there was a voluntary exercise group with unrestricted access to the running wheel for 24 hours. All animals were sacrificed at the end of the exercise regimens. 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. Two-way ANOVAs were completed with pattern (forced, voluntary, or inactive control) and intensity (high, low, or unrestricted) as independent variables and either Flt-1 or Flk-1 area fraction as the dependent variable. Findings indicated that regardless of intensity, voluntary exercise, but not forced exercise, significantly increased Flk-1 and Flt-1 expression in the hippocampus. In the cerebellum there was no pattern effect, but low intensity exercise resulted in significantly greater Flk-1 expression compared to both high and unrestricted intensities. Interestingly, in the cerebellum, Flt-1 expression was significantly greater in inactive controls compared to both forced and voluntary exercise conditions.