Effects of high-intensity endurance exercise training in the G93A mouse model of amyotrophic lateral sclerosis

The G93A transgenic mouse has a mutation in copper/zinc superoxide dismutase (CuZnSOD) that results in oxidative stress and motor neuron loss. Endurance exercise training is known to increase antioxidant capacity in skeletal muscle. Therefore, we hypothesized that endurance training may extend onset of disease or survival in the G93A mouse. We examined the effects of high-intensity endurance exercise training (45 min/day, 5 times/week, progressive increase from 9 to 22 m/min) on disease onset and survival in G93A mice. Endurance training did not affect clinical onset, although it hastened death in male mice (P < 0.05). Endurance-trained males had a statistically significant decrease in rotarod performance at 112 days (P < 0.05), whereas sedentary males decreased at 119 days (P < 0.05). Endurance-trained and sedentary females decreased at 126 days and 129 days, respectively (P < 0.05). Female mice lived longer than males (P < 0.05), and there was a trend for hastened clinical onset in males (P = 0.062). We conclude that high-intensity endurance exercise training does not affect onset of clinical symptoms in G93A mice but hastens a decrease in motor performance and death following onset of clinical symptoms in male mice only. In light of a recent report describing increased survival following low-intensity endurance training, it appears that training intensity is an important determinant of survival in the G93A mouse.