Effect of long‐term exercise on GDNF expression and innervation in rat skeletal muscle
Authors: Cintrón‐Colón Alberto F. , Spitsbergen John M. 
Published: June 2021

Sarcopenia is a major cause of frailty and loss of independence in aging individuals. Results of recent studies suggest that changes in neural tissues may contribute to development of sarcopenia. Exercise provides neuroprotection by promoting neurogenesis, decreasing apoptosis, and modulating inflammation, however the mechanisms by which exercise generates these effects are not well understood. Neurotrophic factors are powerful regulators of neuronal maintenance and synaptic strength. Glial cell line‐derived neurotrophic factor (GDNF) is a neurotrophic factor that has been shown to be a potent survival factor for somatic motor neurons that innervate skeletal muscle, but as age continues, GDNF levels in muscle tend to decrease. This study seeks to expand our understanding of the regulatory processes controlling GDNF expression, which will aid in identifying how these processes become disturbed with aging, injury or in neurodegenerative diseases. Our hypothesis is that long‐term exercise will increase GDNF expression, and support neuromuscular junction (NMJ) structures. For these studies Sprague‐Dawley rats (6‐months of age) were exercised, in the form of voluntary running, for 6 months. Controls consisted of an age‐matched sedentary group maintained in cages without access to running wheels. After 6 months of exercise hind‐limb muscles were collected and processed for measurement of GDNF protein content via enzyme‐linked immunosorbent assay. The length and area of motor end plates were quantified via staining with a‐bungarotoxin. Immunohistochemical analysis was performed to detect co‐localization of GDNF and choline acetyltransferase (ChAT), using antibodies against GDNF and ChAT. There was a significant (p ≤ 0.05) increase in length of stained end plates in muscles from exercised rats (36.6 ± 3.5μm) when compared to that in the age‐matched sedentary group (27.6 ± 1.15μm). There was a significant (p ≤ 0.05) increase in area of stained end plates in muscles from exercised rats (616.3 ± 84.9μm2) when compared to that in the age‐matched sedentary group (430.3 ± 30.8μm2). We also observed a trend towards an increase GDNF protein content in muscle from exercised rats compared to tissues from sedentary control rats; however, the effect was not significant. Although, co‐localization between GDNF and ChAT appeared more apparent in tissues from exercised rats. These findings suggest that increased physical activity enhances structural neuroplasticity in NMJ elements and may possibly lead to enhanced neuromuscular function. Understanding the activity dependent regulation of neurotrophic factor expression and neural plasticity in the neuromuscular system may help in identifying novel targets for pharmacological development.Support or Funding InformationThis work was supported by a grant from the Faculty Research and Creative Activities Award, Western Michigan University, NIH grant 1 R15 AG022908‐01A2, NSF grant DBI 0552517.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.