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Effects of Exercise: Animal Models


Animal models,such as mdx mice that lack Dys, are the most common models used for research. Mice that lack Dys have elevated plasma CK and undergo a cycle of muscle degeneration and regeneration at weaning which may be due to the increased locomotion and muscle loading.

Eccentric Running

Eccentric running was used to demonstrate the increase fragility of mdx mouse muscle by Viquin et al. Dystrophin negative mdx mice had significantly higher plasma CK before, one hour, and three days following eccentric running compared to normal mice. The elevations in CK were the highest one hour post exercise in the mdx mice suggesting muscle damage.

Brussee et. al. have demonstrated, using Evans blue staining techniques, that mdx mice that performed downhill running had up to a 31 percent increase in degenerating muscle fibers compared to sedentary mdx mice. Normal mice that performed downhill running only showed a zero to three percent increase in degenerating fibers.

Eccentric running has been suggested to create more muscle damage compared to horizontal running in mdx mice and normal mice. Mathur et al. examined transverse relaxation constants (T2) in the lower hindlimbs (bone not included) of mdx mice, using magnetic resonance imaging, before and 48 hours following downhill and horizontal running. Higher T2 values following downhill running indicate greater muscle damage compared to horizontal running.

Dystrophin-deficient muscles may have lost the stability of the muscle cell membrane, and were more susceptible to exercise-induced muscle damage that may lead to apoptosis and necrosis.

Spontaneous Wheel Running

Sandri et al. showed that normal and mdx mice allowed to run spontaneously for one night had significantly higher amounts of apoptotic nuclei compared to mdx non-runners. However, no significant differences were observed comparing both non-runner and runners of normal and mdx mice. Although not significant, there was a trend for sedentary mdx mice to have more apoptotic nuclei than normal sedentary mice.

Hayes et al. also used spontaneous wheel running and mdx mice to determine whether the exercise has beneficial or detrimental effects on muscle function. The results showed that mdx mice ran significantly less distance per week and ran at a significantly slower daily speed compared to normal mice. The exercise resulted in improved resistance to fatigue increased proportion of oxidative fibers, and improvements in force production of the soleus and extensor digitorum longus of exercised mdx mice when compared to sedentary mdx mice.

The results of these studies performed on mdx mice suggest that muscles of these animals are more susceptible to muscle damage caused by eccentric contractions compared to normal mice. Additionally, sedentary mdx mice have a tendency to have more muscle nuclei undergoing apoptosis compared to normal sedentary mice. Moreover, it appears that endurance-training adaptations can be achieved in mdx mice.


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