Abstract
The loss of dystrophin produces a mechanically fragile sarcolemma, causing muscle membrane disruption and muscle loss. The degree to which exercise alters muscular dystrophy has been evaluated in humans with Duchenne Muscular Dystrophy (DMD) and in mouse models including the mdx mouse but with inconsistent findings. We now examined two different levels of exercise, moderate and low intensity, in the mdx mouse model in the DBA2J background. mdx mice at 4–5 months of age were subjected to two different doses of exercise. We found a dose-dependent benefit for low and moderate exercise, defined as 4 m/min or 8 m/min, for 30 minutes three times a week. After six months, exercised mdx mice showed improved tetanic and specific force compared to the sedentary group. We also observed increased respiratory capacity manifesting as greater minute volume, as well as enhanced cardiac function mitigating the decline of fractional shortening that is normally seen. Exercised mdx mice also showed a dose-dependent increase in serum adiponectin with a concomitant reduced adipocyte cross sectional area. These findings identify moderate intensity exercise as a means to improve muscle performance in the mdx DBA2J mice and suggest serum adiponectin as a biomarker for beneficial exercise effect in DMD.
Highlights
Duchenne Muscular Dystrophy (DMD) is an X-linked genetic disorder that causes loss of muscle function beginning in early childhood
Dystrophic mice were exercised with 8 m/min and 4 m/min treadmill exercise regimens, and notably both these regimens are less than the 12 m/min regimen that associates with a worsening of the mdx phenotype
To examine how varying thresholds of aerobic exercise affect dystrophic muscle, we subjected mdx mice to treadmill running over a six-month interval, evaluating two different running speeds. These studies were conducted on mice with established disease with exercise beginning at 4–5 months of age
Summary
Duchenne Muscular Dystrophy (DMD) is an X-linked genetic disorder that causes loss of muscle function beginning in early childhood. With moderate and low intensity exercise, mdx mice exhibited an improvement of skeletal muscle function, attenuation of cardiac dysfunction, and improvement in respiratory capacity, and generally did so in a dose-dependent manner. The maximum force generated by sedentary TA muscle was 269 ± 31 mN, compared to low intensity exercised TA at 381 ± 8 mN and moderate intensity exercised TA at 494 ± 30 mN (Fig. 1C).
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