Glial cell line-derived neurotrophic factor protein content in rat skeletal muscle is altered by increased physical activity in vivo and in vitro.

Current evidence suggests that exercise and glial cell line-derived neurotrophic factor (GDNF) independently cause significant morphological changes in the neuromuscular system. The aim of the current study was to determine if increased physical activity regulates GDNF protein content in rat skeletal muscle. Extensor Digitorum Longus (EDL) and Soleus (SOL) hind limb skeletal muscles were analyzed following 2 weeks of involuntary exercise and 4 h of field stimulation or stretch in muscle bath preparations. GDNF protein content was measured via enzyme-linked immunosorbent assay (ELISA). Two weeks of exercise increased GDNF protein content in SOL as compared to sedentary controls (4.4±0.3 pg GDNF/mg tissue and 3.1±0.6 pg GDNF/mg tissue, respectively) and decreased GDNF protein content in EDL as compared to controls (1.0±0.1 pg GDNF/mg tissue and 2.3±0.7 pg GDNF/mg tissue, respectively). GDNF protein content in the EDL decreased following both field stimulation (56%±18% decrease from controls) and stretch (66%±10% decrease from controls). SOL responded to field stimulation with a 38%±7% increase from controls in GDNF protein content, but showed no change following stretch. Pre-treatment with α-bungarotoxin abolished the effects of field stimulation in both muscles and blocked the effect of stretch in EDL. α-bungarotoxin pre-treatment and stretch increased GDNF protein content to 240%±10% of controls in the SOL. Exposure to carbamylcholine decreased GDNF protein content to 51%±28% of controls in the EDL but not SOL. These results suggest that GDNF protein content in skeletal muscle may be controlled by stretch, where it may increase GDNF protein content, and membrane depolarization/acetylcholine (ACh) which acts to decrease GDNF protein content.