Date of Defense

Spring 4-13-2001


Biological Sciences

First Advisor

John Spitzbergen, Biology

Second Advisor

Erica Wehrwein, Biology


Glial cell line derived neurotrophic factor (GDNF) is a recently discovered neurotrophic factor that has effects on the peripheral nervous system. It has been found to prevent axotomy induced death of motorneurons and rescue motoneuros from natural cell death. There is also evidence showing that abnormal expression of GDNF can have devastating effects, either leading to or s found to be linked with neurodegenerative diseases. Presently, little is known about the processes regulating GDNF expression in skeletal muscle. Studying changes in GDNF expression in skeletal muscles grown in culture can aid in understanding these processes. This new information can lead to understanding how these processes can be disturbed from injury or neurodegenerative disease. It can also lead to identifying possible ways pharmacological intervention can slow or reverse abnormal changes following injury or disease. One hypothesis tested states that changes in neurotransmitter release associated with neuromuscular activity will change GDNF expression. To test this, cells were treated with acetylcholine (ACh) and samples were taken at chosen time points. It was found that ACh inhibits GDNF expression. Another hypothesis tested states that depolarization of the skeletal muscle affects GDNF expression. A high concentration of KCl treatment was used to test this hypothesis. It was found that depolarization mimics the effects of ACh, inhibiting GDNF expression. A third hypothesis states that Ca2+ influx influences GDNF expression. This was tested by using the nifedipine to block the Ca2+ influx. It was expected that nifedipine wouold block the inhibiting effects of ACh and have no effect alone, however the concentration used was high and likely had an effect on the results.

Access Setting

Honors Thesis-Campus Only