EXERCISE IS NEUROPROTECTIVE TO MOTONEURON DENDRITES FOLLOWING PARTIAL MOTONEURON DEPLETION VIA A MECHANISM DEPENDENT ON ANDROGEN RECEPTORS AT THE TARGET MUSCLE

Abstract

Motoneuron loss is a severe medical problem that can result in loss of motor control and eventually death. It has been previously demonstrated that partial motoneuron loss can result in dendritic atrophy and functional deficits in nearby surviving motoneurons, and that treatment with testosterone attenuates these structural and functional deficits. In this dissertation, I establish that exercise following partial motoneuron depletion is similarly neuroprotective to motoneurons, via a mechanism that requires androgen receptor activation at the target muscle of the affected motoneurons. I also establish that exercise transiently upregulates both circulating concentrations of testosterone and the density of androgen receptors in quadriceps musculature. Finally, I demonstrate that prior training with exercise is not able to confer resilience to subsequent neural injury, but that exercise may confer androgen sensitivity to a previously insensitive neuromuscular system. The findings in this dissertation demonstrate that exercise is neuroprotective to motoneurons via the same mechanism of androgen receptor activation in the target muscle seen with supplemental hormone treatment, and that a behavioral intervention such as exercise can have modulatory effects on both peripheral and central aspects of the neuromuscular complex.