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 (CON4 week, n = 5 and CON6 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.