Date of Award

8-1-2005

Degree Type

Restricted Access Dissertation

Degree Name

Doctor of Philosophy

Field of Study

Biomedical Sciences

Department

Graduate School of Biomedical Sciences

First Advisor

Michael Forster

Second Advisor

Joan F. Carroll

Third Advisor

Susan Franks

Abstract

Taylor, Sara A., The effect of exercise training on behavior and oxidative stress in aging mice. Doctor of Philosophy (Biomedical Sciences), August 2005, 136 pp., 17 figures, bibliography, 97 titles. Purpose: Accrued oxidative damage to brain tissue is a proposed mechanism of cognitive deficits observed in aging. In mammalian tissue, it is hypothesized that a balance normally exists between pro-oxidants (reactive oxygen/nitrogen species) and endogenous antioxidant enzymes that are able to inhibit the activity of reactive oxygen/nitrogen species. As long as this balance is maintained, oxidative damage is moderated, but if the production of pro-oxidants becomes excessive or if the activity of antioxidants lags, oxidative stress and ultimately oxidative damage to tissues may result. It is the hypothesis of this project that exercise training is able to prevent decreased antioxidant activity in brain tissue, produce a favorable shift in the pro-oxidant/antioxidant balance, and thus moderate oxidative damage in the aging mice brain. Methods: 3 and 20 month old C57BL/6 mice were either subjected to 8 weeks of treadmill exercise followed by 3 weeks of concurrent exercise and behavior testing, or else they were age-matched, non-exercised controls. Mice were tested on multiple behavioral tasks that tested sensorimotor learning as well as tasks that required utilization of various component of cognitive learning. After exercise and behavior testing regimens were completed, biochemistry assays for protein oxidative damage as well as for antioxidant enzyme activity were performed on several brain regions. Results: It is a finding of the study that moderate, short-term exercise initiated in aged C57BL/6 mice resulted in increased fitness in the aged mice to the same degree as observed in young mice, improved some psychomotor skills, including bridge-walking and reaction time, and improved age-impaired spatial memory performance. Moreover, exercise training showed a lack of effect on oxidative damage in all brain regions, increased activity of glutathione peroxidase in the cerebellum and striatum of young, but not aged mice, and it increased the activity of catalase in the cortex of aged mice. Conclusions: The data presented in this project shows that exercise does moderate some age associated cognitive deficits, and the findings do not preclude the possibility that exercise produces this effect by reducing accrued oxidative damage that occurs with aging.

Comments

Taylor, Sara A., The effect of exercise training on behavior and oxidative stress in aging mice. Doctor of Philosophy (Biomedical Sciences), August 2005, 136 pp., 17 figures, bibliography, 97 titles. W 4 T246E 2005

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