The effect of exercise on markers of oxidative stress in a mouse model of ALS

Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease associated with oxidative stress. G93A mice are a transgenic strain that overexpress mutant CuZn superoxide dismutase (SOD1mut) and are a model for ALS. Endurance exercise increases antioxidant capacity in healthy skeletal muscle; however, it is unclear whether exercise is beneficial or deleterious in disorders with inherently high oxidative stress. We examined the effect of endurance exercise on markers of oxidative stress including malondialdehyde (MDA), protein carbonyls and mitochondrial superoxide dismutase (MnSOD) protein content in transgenic (B6SJL‐Tg (SOD1‐93A)1Gur/J) and wildtype (WT) mice. Animals were randomly assigned to endurance exercise‐training (TRA, n=8) or sedentary (SED, n=8) groups. Mice trained on a treadmill 45min/d, 5x/wk, 22m/min for 8 wk and were sacrificed at 110 d, red and white m. gastrocnemius samples were analyzed. MDA and protein carbonyls were both higher in red and white muscle for TRA as compared to SED G93A mice (p<0.05). Exercise training did not alter the level of MDA or carbonyls in red or white muscle of WT mice but did increase MnSOD protein content in white but not in red muscle (p<0.05). MnSOD protein content was higher in G93A as compared to WT mice (p<0.001). We conclude that exercise‐training is not associated with increased oxidative damage in WT mice, possibly due to induction of MnSOD. In contrast, the upregulation of MnSOD in G93A mice is not able to protect their muscle during super‐imposed exercise stress possibly due to constitutive overproduction of RONS. (Funded by Warren Lammert and family).