Voluntary exercise decreases progression of muscular dystrophy in diaphragm of mdx mice

Abstract

Effects of voluntary wheel running on contractile properties of diaphragm (DIA) and soleus (SOL) of dystrophic (mdx) and control (C57BL/10SNJ) mice were evaluated. In particular, we tested the hypothesis that daily voluntary running is not deleterious to muscle function in mdx mice. Both groups of mice ran extensively (control mice approximately 7 km/day, mdx mice approximately 5 km/day). Exercise increased maximal specific tetanus tension of mdx DIA from 1.02 +/- 0.04 to 1.33 +/- 0.06 kg/cm2 but did not restore it to the control level (2.55 +/- 0.17 kg/cm2). Maximal tetanus tension of sedentary mdx SOL (2.41 +/- 0.17 kg/cm2) was reduced compared with control (3.10 +/- 0.15 kg/cm2) and was not altered by running activity. Optimal length was significantly lower in DIA of mdx mice, and exercise did not change this. Fatigability and contractile properties of muscles measured in vitro were not altered by running activity with the exception of increased contraction time in mdx DIA. In conclusion, extensive wheel running is not deleterious to muscle function in mdx mice contrary to predictions of the "work overload" theory of muscular dystrophy. Rather, this exercise is beneficial for active tension generation of mdx DIA, the muscle most closely resembling muscles of patients with Duchenne muscular dystrophy.

Skeletal muscle adaptations in response to voluntary wheel running in myosin heavy chain null mice

“…In the mdx mouse, a transgenic model with significant muscle degeneration/regeneration and muscle pathology, there is conflicting evidence regarding the effects of exercise. Specifically, voluntary wheel running has been shown to increase muscle force output and decrease muscle fatigability (16,23), whereas eccentric exercise has been shown to be significantly more damaging to mdx muscle than to control muscle (11). An additional question regarding the MHC null mice, therefore, was whether wheel-running activity would affect the muscle pathology observed in these animals.…”

Decreased Mitochondrial Oxygen Consumption and Antioxidant Enzyme Activities in Skeletal Muscle of Dystrophic Mice after Low-Intensity Exercise

“…Compared to previous experimental exercise protocols, in which voluntary running resulted in shorter running distances for mdx than for genetically unaffected mice [8,15], the exercise protocol used in the present investigation was standardised for both control and mdx mice.…”

Regenerative capacity of the dystrophic (mdx) diaphragm after induced injury

“…In support of this hypothesis, Barton et al (4) have shown that overexpression of insulin-like growth factor I in mdx mice augments muscle mass and reduces fibrosis within the diaphragm. Second, there is evidence that short-term strength or endurance training is useful for reducing the loss of diaphragmatic force-generating capacity and increased muscle fatigability associated with dystrophin deficiency (8,10,50). However, there has also been a fear that training could increase the level of contraction-induced injury and hence satellite cell turnover, thereby leading to an accelerated decline of regenerative potential (39).…”