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Abstract

St8Sia2 gene overexpression in mice simulates a human-like mutation which occurred through the process of evolution more than 100,000 years ago. This mutation results in longer polysialic acid chains on the surface of cells. Polysialic acid chains play a role in cell-cell signaling, particularly in the hippocampus, due to the ability to bind to growth factors including brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF-2). Exercise is a well-known stimulus in increasing hippocampal neurogenesis through BDNF. Therefore, We hypothesized that overexpression of ST8Sia2 would improve the exercise training response and augment exercise-induced neurogenesis. Male and female wild type, heterozygous ST8Sia2(+/–), and homozygous ST8Sia2(+/+) mice were exercise tested on a treadmill for speed and endurance before and after a 2-week period of voluntary exercise training. Male mice showed an overall exercise training response in both speed (p=0.01) and endurance (p=0.004) tests but no genotype effect (speed, p=0.39; endurance, p=0.14). Female mice exhibit both training and genotype effects in speed (training, pST8Sia(+/–) mice revealed a specific increase in speed (p=0.0005) and endurance (p=0.006) with exercise training that was blunted in ST8Sia2(+/+) [speed (p=0.03), endurance (p=0.001)]. Mice have been BrDU treated and cerebral samples have been collected for future analysis of exercise-induced neurogenesis. Overall, these data suggest that overexpression of ST8Sia2 does not have a positive effect on exercise performance, and at high expression levels may even decrease in exercise capacity in female mice, but the mechanism behind the possible decrease in exercise capacity has not yet been identified. We are currently in the process of imaging brain sections using confocal microscopy to determine if there is an increase or decrease in neurogenesis in ST8Sia2(+/–) and the ST8Sia2(+/+) mice that accompany these gender-specific exercise responses.

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