Exercise-induced plasticity in the central nervous system of aged and injured animals.

摘要

Plasticity in the central nervous system (CNS) is a known mechanism of remodeling in response to many different stimuli. In this dissertation, the idea that exercise can induce plasticity in the CNS was explored in two different models, aging and injury. To that end, this dissertation asks whether exercise is effective in improving behavior after chronic neurodegeneration, in an aging animal, and after traumatic neurodegeneration, in an injured animal. In the aging model, the behavioral effects of exercise were investigated in young and aged animals and plasticity-related genes were assayed in the hippocampus to determine if there were age and/or exercise effects. In the injury model, moderate thoracic spinal cord injury (SCI) was used in an animal model to test the hypothesis that exercise improves locomotor recovery after SCI. Trophic factors and neurogenesis in the spinal cord were measured after three weeks of wheel running as potential mechanisms induced by pre-injury running which could contribute to improved locomotor recovery. Finally, a clinically relevant investigation of post-injury exercise was used to determine if fiber sprouting contributed to the improved locomotor recovery. The results of this work show that exercise induces plasticity in both models of normal aging and traumatic spinal cord injury. Aged animals improved performance on a retention task which correlated with exercise-induced changes in hippocampal learning and memory genes. However, changes in synaptic genes were not observed in the absence of the learning task, i.e., with exercise alone. Exercise also improved locomotor recovery after SCI in an animal model. Running wheels modified to have a flat-surface improved locomotor recovery after SCI. Investigations of post injury exercise demonstrated that both three and seven days/week were sufficient to improve recovery. While no pre-injury mechanisms were identified, post injury exercise increased serotonergic fibers caudal to the lesion, a mechanism correlated to improved locomotor recovery in other work. The data demonstrate that exercise improves behavior and thus induces plasticity in the CNS in models of chronic neurodegeneration, aging, and traumatic neurodegeneration, SCI.