GDNF content and NMJ morphology are altered in recruited muscles following high‐speed and resistance wheel training

Abstract Glial cell line‐derived neurotrophic factor ( GDNF ) may play a role in delaying the onset of aging and help compress morbidity by preventing motor unit degeneration. Exercise has been shown to alter GDNF expression differently in slow‐ and fast‐twitch myofibers. The aim was to examine the effects of different intensities (10, 20, ~30, and ~40 m·min −1 ) of wheel running on GDNF expression and neuromuscular junction ( NMJ ) plasticity in slow‐ and fast‐twitch myofibers. Male Sprague‐Dawley Rats (4 weeks old) were divided into two sedentary control groups ( CON 4 week, n  = 5 and CON 6 week, n  = 5), two involuntary running groups, one at a low velocity; 10 m/min ( INVOL ‐low, n  = 5), and one at a higher velocity; 20 m/min ( INVOL ‐high, n  = 5), and two voluntary running groups with resistance ( VOL ‐R, n  = 5, 120 g), and without resistance ( VOL ‐ NR , n  = 5, 4.5 g). GDNF protein content, determined by enzyme‐linked immunosorbent assay ( ELISA ), increased significantly in the recruited muscles. Plantaris ( PLA ) GDNF protein content increased 174% ( P  <   0.05) and 161% ( P  <   0.05) and end plate‐stained area increased 123% ( P  <   0.05) and 72% ( P  <   0.05) following VOL ‐R, and VOL ‐ NR training, respectively, when compared to age‐matched controls. A relationship exists between GDNF protein content and end plate area ( r  = 0.880, P  < 0.01, n  = 15). VOL ‐R training also resulted in more dispersed synapses in the PLA muscle when compared to age‐matched controls ( P  <   0.05). Higher intensity exercise (>30 m/min) can increase GDNF protein content in fast‐twitch myofibers as well as induce changes in the NMJ morphology. These findings help to inform exercise prescription to preserve the integrity of the neuromuscular system through aging and disease.