Date of Award

4-2014

Degree Name

Doctor of Philosophy

Department

Biological Sciences

First Advisor

Dr. John M. Spitsbergen

Second Advisor

Dr. Christine Byrd-Jacobs

Third Advisor

Dr. Christopher Pearl

Fourth Advisor

Dr. Christopher Cheatham

Keywords

Skeletal muscle, slow twitch, GDNF, fast twitch, neuromuscular junction (NMJ)

Abstract

Glial cell-line derived neurotrophic factor (GDNF) supports and maintains the neuromuscular system during development and through adulthood by promoting neuroplasticity. GDNF may play a role in delaying the onset of aging and help compress morbidity by preventing motor unit degeneration. Exercise has been shown to alter GDNF expression differently in slow and fast twitch myofibers. The aim of this dissertation project is to determine if different intensities of exercise can promote changes in GDNF expression and neuromuscular junction (NMJ) morphology in slow and fast twitch muscle fibers. Skeletal muscle fibers were analyzed from adult Sprague Dawley rats aged 4 weeks old and 6 months old. The phenotype of the skeletal myofibers analyzed are from predominantly slow motor units (soleus; SOL) and fast motor units (extensor digitorum longus; EDL and plantaris; PLA). Animals were exercised through voluntary and involuntary means in a swimming barrel and a running wheel with and without resistance for two weeks. The intensity of exercise was altered by different modes of exercise as well as different running speeds and with the use of resistance. GDNF protein content was determined by enzyme-linked immunosorbant assay and immunohistochemistry was utilized to determine myofiber size, end plate measurements, and localization of GDNF. GDNF protein content was increased (P < 0.05) in all recruited myofibers including; slow twitch myofibers (SOL) following all training protocols and fast twitch myofibers (PLA) following higher intensity exercise such as running at speeds faster than 30m/min. Although not significant, GDNF increased 60% in fast twitch EDL myofibers following swim-training. A relationship exists between GDNF protein content and end plate area. These results indicate that GDNF protein content is upregulated in skeletal muscle fibers that are recruited to meet the demands of the given task, in an activity-dependent manner, and induce neuroplasticity at the neuromuscular junction. These findings help to inform exercise prescription to preserve the integrity of the neuromuscular system through aging, injury, and disease.

Access Setting

Dissertation-Open Access

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