Dissertation Defenses

Doctoral Dissertation Announcement

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Candidate: Nathan Peplinski

Degree of: Doctor of Philosophy

Department: Biological Sciences

Title: The Effects of Aging and Activity on Glial Cell Line- derived Neurotrophic Factor Expression in Skeletal Muscle

Committee:
Dr. John Spitsbergen, Chair
Dr. John Jellies
Dr. William Jackson
Dr. Tom Gorczyca

Date: Tuesday, July 10, 2007 10:00 a.m. – 12:00 p.m.
1728 Wood Hall

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 analyzed the GDNF protein content of rats from one month of age through 23 months of age. We found that GDNF expression was highest at one month of age when the nerve and muscle have recently completed their developmental changes and significantly decreased by early adulthood. GDNF expression was not significantly altered throughout the majority of adulthood until it significantly increased at the oldest time points of 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 the skeletal muscle studied. We also determined that if we blocked the receptors for the neurotransmitter (which is released by the motor neuron) and stimulated skeletal muscle to contract, there was no significant change in GDNF protein content. This suggested that receptor activation was needed for changes in GDNF to occur. When we added an agonist to directly activate these receptors, without electrically stimulating the muscle, GDNF protein expression was altered in a similar manner as with electrical stimulation alone. Together these results suggest that these receptors are involved the regulation of GDNF protein expression with activity. These results provide a better understanding of how GDNF protein expression is regulated in skeletal muscle.