Date of Defense

4-1-2015

Date of Graduation

5-2015

Department

Biological Sciences

First Advisor

John Spitsbergen

Second Advisor

Christine Byrd-Jacobs

Third Advisor

Amy Gyorkos

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease accompanied by the loss of motor neurons, leading to paralysis and death. Glial cell line-derived neurotrophic factor (GDNF) promotes neuron health and function and has been proposed as a therapeutic treatment for ALS. GDNF protein expression in skeletal muscle is regulated by physical activity. The aim of this study was to determine if low intensity exercise would increase GDNF expression in skeletal muscle and slow degeneration of motor neurons in a mouse model of ALS. Following the first sign of disease onset, transgenic ALS mice were randomly assigned to one of three groups: sedentary control, involuntary low intensity exercise, and involuntary low intensity exercise with anti-GDNF injections, twice daily. Anti-GDNF injections were administered to determine if neutralizing GDNF inhibited the beneficial effects of exercise on the motor nervous system. Neurological score was tested daily throughout the exercise protocol, and animals were euthanized at 115 days of age. Lumbar spinal cord, soleus, and pectoralis major muscles were removed and analyzed for GDNF content by enzyme-linked immunosorbant assay. Immunohistochemical analysis of spinal cord was performed to assess motor neuron cell body count. Histological analysis of skeletal muscle was performed to examine endplate area and location of GDNF. Onset of neurological symptoms appeared to be delayed in the exercise group, when compared to the sedentary control and exercise with anti-GDNF treatment groups, although this was determined not to be statistically significant. GDNF content was not significantly affected in spinal cord, soleus, or pectoralis major, although there was a trend towards an increase in the exercised group compared to the control and anti-GDNF group. Histological analysis of spinal cord sections revealed a significant (p

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Honors Thesis-Open Access

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