Date of Award

4-2013

Degree Name

Doctor of Philosophy

Department

Biological Sciences

First Advisor

Dr. John M. Spitsbergen

Second Advisor

Dr. Christine Byrd-Jacobs

Third Advisor

Dr. Cindy Linn

Fourth Advisor

Dr. Damon Miller

Abstract

Neurotrophic factors may play a role in exercise-induced neuroprotective effects; however, it is not known if exercise mediates changes in glial cell line-derived neurotrophic factor (GDNF) protein levels in the spinal cord. The aim of the studies described herein was to determine if exercise alters GDNF protein expression in the lumbar spinal cord of healthy and diseased animals. The lumbar spinal cord was analyzed from adult rats aged 6-, 12-, 18- and 24-months, and from transgenic amyotrophic lateral sclerosis (ALS) mice and wild-type mice aged 3 months. Animals had undergone either forced wheel running, voluntary wheel running or swimming for either 2- or 4-weeks or 6 months in duration. GDNF protein was quantified via enzyme-linked immunosorbent assay and Western blot. Immunohistochemical analysis localized GDNF in choline acetyltransferase (ChAT)-positive motor neurons and cell body areas were measured. Results indicate that short-term exercise (2 weeks) increases GDNF protein content in the rodent lumbar spinal cord. Chronic exercise (4 weeks to 6 months) has no effect on GDNF protein content in the rodent lumbar spinal cord. All exercise protocols increased the size of ChAT-positive motor neuron cell body areas of healthy, non-diseased animals. Treatment with neutralizing antibodies for GDNF in the transgenic ALS animals blocked the beneficial effects of exercise on motor neurons. These results suggest that short-term exercise elicits an increase in neurotrophic factors via an activity-dependent relationship that occurs with GDNF protein expression in spinal cord. Understanding how neurotrophic factors are regulated by physical activity is crucial for maintaining a healthy motor nervous system and for developing therapies for individuals with compromised motor nervous systems, e.g. due to aging or disease.

Access Setting

Dissertation-Open Access

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