Exercise training improves plantar flexor muscle function in mdx Mice

Purpose: We tested the hypothesis that low-intensity exercise in mdx mice improves plantar flexor muscle contractile function, resistance to fatigue, and mitochondrial adaptations without exacerbating muscular dystrophy. Methods: We subjected mdx mice to 12 wk of voluntary low-resistance wheel running (Run, n = 17) or normal cage activities (sedentary (Sed), n = 16) followed by in vivo analyses for plantar flexor torque generation and fatigue resistance or running capacity on a treadmill. Gastrocnemius muscles were further evaluated for exercise-induced mitochondrial adaptations and fiber type distribution and central nuclei. t-tests were used to determine differences between the Sed and Run groups. Results: Plantar flexor submaximal isometric torques and maximal isometric torque at multiple ankle joint angles and resistance to fatigue were greater in Run compared with Sed mdx mice (P < 0.05). Citrate synthase and β-hydroxyacyl-CoA dehydrogenase enzyme activities and cytochrome c oxidase IV protein expression in gastrocnemius muscles were greater in Run than in Sed mdx mice (P ≤ 0.04), along with a trend of fiber type transformation from Type IIb to Type IIx fibers. Exercise training in mdx mice did not elevate serum creatine kinase levels but led to a significant reduction of centrally nucleated myofibers. Conclusions: Voluntary low-resistance wheel running in mdx mice can result in skeletal muscle adaptation, leading to improved contractile function and reduced fatigability, with no indication that exercise was detrimental. This study supports the need for further investigation of low-intensity exercise as an early therapeutic intervention in ambulatory boys with Duchenne muscular dystrophy.