Monica McCullough

Doctoral Dissertation Announcement

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Candidate: Monica McCullough

Degree of: Doctor of Philosophy

Department: Biological Sciences

Title: Exercise Alters Glial Cell Line-derived Neurotrophic Factor (GDNF) Protein Expression in the Spinal Cord

Committee:
Dr. John Spitsbergen, Chair
Dr. Christine Byrd-Jacobs
Dr. Cindy Linn
Dr. Damon Miller

Date: Wednesday, February 20, 2013 11 a.m. to 1 p.m.
2734 Wood Hall

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 studies described herein have been designed to determine if exercise alters GDNF protein expression in the lumbar spinal cord of healthy and diseased animals.  Animals undergo forced wheel running, voluntary wheel running, or swimming for either 2- or 4-weeks or 6 months in duration.  The lumbar spinal cord is 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.  GDNF protein is quantified via an enzyme-linked immunosorbent assay and Western blot.  Immunohistochemical analysis localized GDNF in choline acetyltransferase (ChAT)-positive motor neurons and cell body areas are measured.  Results from these studies indicate that short-term exercise of 2 weeks increases GDNF protein content in the rodent lumbar spinal cord.  Chronic exercise of 4 weeks to 6 months has no effect on GDNF protein content in the rodent lumbar spinal cord. All exercise protocols increase 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 blocks the beneficial effects of exercise on motor neurons.  In conclusion, these results suggest an activity-dependent relationship that occurs with GDNF protein expression in spinal cord, where short-term exercise elicits an increase in neurotrophic factors compared to long-term exercise. Understanding how neurotrophic factors are regulated by physical activity are crucial for maintaining a healthy motor nervous system and for developing therapeutic strategies for individuals with compromised motor nervous systems, such as aging or disease.