GDNF is regulated in an activity‐dependent manner in rat skeletal muscle

Glial cell line–derived neurotrophic factor (GDNF) is produced by skeletal muscle and affects peripheral motor neurons. Elevated expression of GDNF in skeletal muscle leads to hyperinnervation of neuromuscular junctions, whereas postnatal administration of GDNF causes synaptic remodeling at the neuromuscular junction. Studies have demonstrated that altered physical activity causes changes in the neuromuscular junction. However, the role played by GDNF in this process in not known. The objective of this study was to determine whether changes in neuromuscular activity cause altered GDNF content in rat skeletal muscle. Following 4 weeks of walk‐training on a treadmill, or 2 weeks of hindlimb unloading, soleus, gastrocnemius, and pectoralis major were removed and analyzed for GDNF content by enzyme‐linked immunosorbant assay. Results indicated that walk‐training is associated with increased GDNF content. Skeletal muscle from hindlimb‐unloaded animals showed a decrease in GDNF in soleus and gastrocnemius, and an increase in pectoralis major. The altered production of GDNF may be responsible for activity‐dependent remodeling of the neuromuscular junction and may aid in recovery from injury and disease. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 206–211, 2002