NRSA FOR PAMELA COBURN-LITVAK: GLUCOCORTICOIDS VS. EXCERISE IN HIPPOCAMPUS

Prolonged exposure to glucocorticoids (GC's) impairs spatial learning, a hippocampus-related task; decreases growth factor expression, and induces hippocampal dendritic atrophy. In contrast, exercise enhances spatial learning, increases growth factor expression, and induces hippocampal cell proliferation and survival. In the proposed study, Hypothesis 1 states that GC treatment will reduce the number of synapses in the hippocampus, which has not been directly tested. Hypothesis 2 states that exercise will attenuate GC- induced hippocampal synapse loss and spatial impairment. While this has not yet been tested in the hippocampus, exercise has been shown to attenuate GC-induced atrophy in the skeletal muscle To address Hypothesis 1, one group of animals will receive glucocorticoid injections; the other group will receive vehicle injections. To address Hypothesis 2, two groups of animals will voluntarily exercise prior to receiving GC or vehicle injections; two other groups will remain sedentary. GC-mediated spatial impairments as well as possible attenuation of impairment by exercise will be behaviorally tested in the Y maze. Unbiased stereologically methods will be used to estimate GC-mediated changes in synapse numbers and possible attenuation of synapse loss by exercise. Elevated GC levels accompany a variety of neuroendocrine and neuropsychiatric of disorders as well as the aging process. Millions of individuals also take prescription GC's to control autoimmune and allergy symptoms. Exercise is proposed as a possible preventative measure against the structural and cognitive damaged caused by chronically elevated GC's.