Exercise and the Aged Brain: Neurotrophins and Stress

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DESCRIPTION (provided by applicant): As the average age of citizens in the United States increases each year with the large number of people from the baby boomer generation reaching retirement age, the number of patients with age-associated neurological problems increases. For example, it is estimated that if no effective treatments, preventative approaches or cures are developed for Alzheimer's disease (AD), that the number of AD patients will more than triple in the next 40-50 years. Other age related disorders, such as Parkinson's disease, depression and overall decline in learning and memory processes will show similar dramatic increases in number of people afflicted. The proposed AREA project uses an animal model to address this issue by characterizing the effects of physical exercise on the rat brain, in particular on the expression of endogenous biochemical's responsible for nourishing and maintaining the overall health of neurons, neurotrophins. The project will be conducted at the University of Colorado at Denver (UCD), which is an urban university that serves many non-traditional students, trains significant numbers of graduates who pursue careers in the biomedical sciences, and is not a major recipient of NIH support. This AREA project utilizes the aged rat, an animal model for human aging that has been extensively studied in relation to the decline in cognitive function seen in senescence. Previous reports in the literature have found that voluntary exercise in young or middle aged rats enhances neurotrophin mRNA levels. However, no reports have been published studying exercise effects in the aged rat brain. Specific Aim 1 seeks to determine if exercise enhances neurotrophin expression in the aged rat brain by systematically examining the time course of exercise induced changes in nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) mRNA and protein expression. Specific Aim 2 will assess the level of stress voluntary versus forced physical exercise causes in rats of various ages, and how this impacts NGF and BDNF expression. Specific Aim 3 will test the effect of exercise on learning and memory tasks in the aged rats and seeks to correlate neurotrophin levels in the brain with behavioral performance. Future studies will test the impact of physical exercise on neurotrophin expression in the brain and on animal models of age-associated neurological disorders found in humans, in which up regulation of levels of endogenous neurotrophins may be therapeutic. Possible disorders include Parkinson's disease and depression. This project will establish a new and productive research program that will provide increased research opportunities for UCD students.