Date of Defense

4-18-2014

Date of Graduation

4-2014

Department

Biological Sciences

First Advisor

John Spitsbergen

Second Advisor

Cindy Linn

Third Advisor

Amy Gyorkos

Abstract

Neurotrophic factors are proteins that play an important role in the development and maintenance of neurons. Recent studies have shown that neurotrophic factors may hold promise for treating damage to the nervous system caused by trauma or diseases, such as amyotrophic lateral sclerosis or Parkinson’s disease. Glial cell line-derived neurotrophic factor (GDNF) is expressed in skeletal muscles and affects peripheral motor neurons. Results of previous studies have demonstrated that exercise can increase GDNF content in skeletal muscle of rat. The goal of the current study was to examine whether expression of GDNF in skeletal muscle of mouse is also regulated by physical activity. Our hypothesis states that muscles undergoing higher levels of contractile activity will express GDNF at higher levels than muscle exhibiting lower levels of contractile activity. For these studies we examined GDNF protein content in tissues from sedentary control mice and in mice following exercise. Muscles examined included the diaphragm (DIA), an involuntary slow twitch muscle and pectoralis major (PEC), a voluntary slow twitch muscle. Treatment groups included 7 control mice and 6 mice that underwent walk training. The treatment group had a one-week training period, and then exercised for 30 minutes a day, at 8 meters/minute, five days a week. Following completion of the exercise regimen muscles were removed and processed for determination of GDNF protein content using enzyme-linked immunosorbant assay, GDNF protein localization and end plate morphology. The results show that DIA from control animals contains more GDNF than PEC, while exercise increased GDNF protein content in PEC but not DIA. These findings suggest that GDNF production is effected by exercise in voluntary slow-twitch muscles, but not involuntary slow-twitch muscles. These results contribute to understanding the mechanisms underlying the normal control of GDNF expression in skeletal muscles. It is important to develop a more complete understanding of normal expression of GDNF in skeletal muscle before we can determine whether GDNF-based therapies may be used in the treatment of traumatized or diseased neural tissues.

This work was supported by a grant from the Faculty Research and Creative Activities Award, Western Michigan University, NIH grant 1 R15 AG022908-01A2, NSF grant DBI 055251, the Lee Honors College, the Office of Vice President for Research (OVPR) Undergraduate Research Excellence Award, and the College of Arts and Sciences Research and Creative Activities Award at Western Michigan University.

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Honors Thesis-Open Access

Erin Donovan LHC Thesis Presentation.pdf (1935 kB)
Powerpoint Presentation

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