Faculty Mentor

Dr. John Spitsbergen


Biological Sciences

Presentation Date


Document Type



Glia cell line-derived neurotrophic factor (GDNF) is a potent survival factor for sub-populations of neurons including somatic and autonomic motor neurons. These neurons depend, in part, on GDNF that is synthesized and secreted by their target tissues. Whether the processes regulating GDNF production in these tissues is similar or different is poorly understood. The current study compares the regulation of production of GDNF in skeletal muscle and cardiac muscle following electrical and chemical stimulation. We show that electrical stimulation has opposing effects on GDNF production in cardiac and skeletal muscle, where GDNF levels increase with long-term electrical stimulation in skeletal muscle and decrease with the long term electrical stimulation in cardiac muscle. An increase in GDNF levels from 13% to 128% of control was observed in skeletal muscle following 1 and 5Hz stimulation, respectively, whereas in cardiac cells, there was a rapid reduction in GDNF levels in cells that were stimulated at 5Hz. Conversely, treatment with acetylcholine leads to inhibition of GDNF production in both cardiac and skeletal muscle cells. Treatments of 1μM acetylcholine reduced GDNF secretion by 27% and 66% in skeletal muscle and cardiac muscle, respectively. Treatment with 100 μM acetylcholine caused a decline in GDNF levels by 34% and 91% in skeletal muscle and cardiac muscle, respectively. The current results suggest that GDNF expression may be differentially regulated in the heart and skeletal muscle. Understanding the regulation of GDNF production in these target tissues will provide a better understanding of how these processes may be modulated therapeutically.