Date of Award

8-2007

Degree Name

Doctor of Philosophy

Department

Biological Sciences

Abstract

Glial cell line-derived neurotrophic factor (GDNF) is an extracellular signaling protein that is produced by skeletal muscle and is important for the motor neurons that control muscle movement. GDNF has been shown to keep neurons alive under conditions that they would otherwise not persist. In skeletal muscle, GDNF has been shown to be one of the most potent neurotrophic factors that influence motor neuron survival. While the role of GDNF has been well studied during early development, not much is known about what happens to GDNF expression in the adult and with advanced aging. Previous results from our lab have demonstrated that GDNF protein content in the adult can be significantly altered with exercise. It was the purpose of these studies to determine the effects of aging and activity on GDNF protein expression in rat skeletal muscle.

We found that GDNF expression was not significantly altered throughout the majority of adulthood until it significantly increased at 19 and 23 months of age. This time frame overlaps with onset of sarcopenia (age-related muscle loss and weakness). We also found that changes in GDNF, both in early and in late-life stages, appeared to be specific to skeletal muscle type. These results suggest that changes in GDNF and/or its ability to signal to motor neurons may be involved in age-related changes that occur in skeletal muscle.

Additionally we investigated how GDNF expression is altered with activity. When we stimulated skeletal muscle to contract we observed significant changes in GDNF protein content in skeletal muscle. Again we found that these responses were specific to skeletal muscle type. Further investigation determined that the receptors for the neurotransmitter, acetylcholine, appeared to be involved in the regulation of GDNF protein expression with activity. These results provide a better understanding of how GDNF protein expression is regulated in skeletal muscle.

Access Setting

Dissertation-Open Access

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