GDNF expression is increased in denervated human skeletal muscle

Area of Science:

• Neuroscience
• Molecular Biology
• Muscle Physiology

Background:

• Glial cell line derived neurotrophic factor (GDNF) supports motor neuron survival.
• Two GDNF gene transcripts (GDNF633 and GDNF555) are found in skeletal muscle.
• GDNF upregulation in rat muscle after denervation suggests a role in muscle response to nerve injury.

Purpose of the Study:

• To investigate GDNF transcript expression in human skeletal muscle.
• To determine GDNF's role in neuromuscular diseases like Duchenne muscular dystrophy and denervation.
• To explore the relationship between GDNF levels and muscle atrophy severity.

Main Methods:

• Analysis of GDNF expression using competitive RT-PCR in 38 human muscle specimens.
• Comparison of GDNF levels in normal, denervated, and Duchenne muscular dystrophy muscle.
• Morphometric analysis of muscle fiber calibers correlated with GDNF expression.

Main Results:

• Both GDNF transcripts were significantly elevated in denervated muscle compared to normal and dystrophic muscle.
• Higher GDNF levels correlated with rapidly progressive neurogenic atrophy, including amyotrophic lateral sclerosis (ALS) cases.
• GDNF transcript levels were not significantly altered in dystrophic muscle compared to controls.

Conclusions:

• Denervation, not muscular dystrophy, enhances GDNF expression in human skeletal muscle.
• Increased GDNF expression is a response to motor nerve lesion and denervation.
• GDNF may promote nerve fiber regeneration and muscle reinnervation.