Age-related Changes in GDNF Content of Skeletal Muscle

Stephanie Elise Jerger


Glial cell line-derived neurotrophic factor (GDNF) is a very potent neurotrophic factor that promotes the maintenance and survival of peripheral motor neurons and is expressed in skeletal muscle. Progressive loss of motor neurons occurs with aging, and over time this degeneration elicits devastating consequences on the physical performance and quality of life of the elderly. One possible explanation for motor neuron degeneration is a reduction in neurotrophic factor support. The primary objective of this study is to examine the age-related changes in GDNF content of skeletal muscle of sedentary Sprague-Dawley rats. Acquiring a better understanding of how GDNF expression in skeletal muscle changes with age will provide insight into the role that GDNF plays during the process of age-induced motor neuron loss. To accomplish this, we are using an inverted confocal scanning microscope to view GDNF protein in the extensor hallucis longus (EHL) skeletal muscle from rats aged 3 weeks to 24 months. The muscles were fixed with paraformaldehyde, and the size and shape of neuromuscular junctions were measured using alpha-bungarotoxin to detect acetylcholine receptors, antibodies against synaptic vesicle protein 2 (SV2) to detect nerve terminal and antibodies against GDNF to determine where and how much GDNF is in the muscle. The results of our study thus far have shown that neuromuscular junctions (NMJ) are immature and undergo initial development in rats aged 3 weeks, and the staining of trophic factor was strongest at this age. The end plates from rats aged 5 and 8 weeks were more developed, and the presence of trophic factor was clearly defined at the end plates. In the EHL muscle from rats aged 24 months, there appeared to be multiple end plates at each fiber, some of which were small and immature, which is indicative of possible degeneration followed by regeneration. Staining for GDNF in rats aged 24 months appeared less defined and dispersed around the NMJ rather than localized at the end plates, which further supports the possibility of end plate degeneration and regeneration. These results suggest that the presence of trophic factor is strongest while the NMJ is forming in young rats, and that the dispersal and decrease of GDNF in old rats appears to correlate with degeneration and regeneration. This work was supported by NIH grant 1 R15 AG022908-01A2, NSF grant DBI 0552517 and Western Michigan University.


GDNF; Aging; Neuromuscular Junctions; Neurotrophic Factors; Skeletal Muscle

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