The effects of concentric and eccentric training in murine models of dysferlin‐associated muscular dystrophy

Abstract

IntroductionDysferlin‐deficient murine muscle sustains severe damage after repeated eccentric contractions.MethodsWith a robotic dynamometer, we studied the response of dysferlin‐sufficient and dysferlin‐deficient mice to 12 weeks of concentrically or eccentrically biased contractions. We also studied whether concentric contractions before or after eccentric contractions reduced muscle damage in dysferlin‐deficient mice.ResultsAfter 12 weeks of concentric training, there was no net gain in contractile force in dysferlin‐sufficient or dysferlin‐deficient mice, whereas eccentric training produced a net gain in force in both mouse strains. However, eccentric training induced more muscle damage in dysferlin‐deficient vs dysferlin‐sufficient mice. Although concentric training produced minimal muscle damage in dysferlin‐deficient mice, it still led to a prominent increase in centrally nucleated fibers. Previous exposure to concentric contractions conferred slight protection on dysferlin‐deficient muscle against damage from subsequent injurious eccentric contractions.DiscussionConcentric contractions may help dysferlin‐deficient muscle derive the benefits of exercise without inducing damage.

Intensive Teenage Activity Is Associated With Greater Muscle Hyperintensity on T1W Magnetic Resonance Imaging in Adults With Dysferlinopathy

“…The method used here to quantify the "amount" of exercise performed used the relative metabolic equivalents of the sports performed, giving an estimate of the intensity of the exercise. However, research in mice suggests that it may be the type of muscle contraction, rather than the metabolic cost, which determines the effect on dysferlin deficient muscle (5,6). Unfortunately we were not able to assess this here because, as anticipated in an observational study, none of our participants had performed exclusively concentric exercise (such as swimming) without also reporting frequent eccentric sports (such as running).…”

“…The association of exercise and disease progression in dysferlinopathy has been investigated in mouse models, with interesting results. Eccentric muscle contractions (such as running) cause more rapid progression of muscular dystrophy pathology and greater functional weakness, while concentric muscle contraction (such as swimming) appeared to be protective against both general disease progression and in mitigating the myofiber damage caused by subsequent eccentric muscle contraction (5,6). This finding clearly has implications for patients in terms of the type or intensity of exercise that should be recommended.…”

“…This finding clearly has implications for patients in terms of the type or intensity of exercise that should be recommended. However, murine models of dysferlinopathy are not particularly good mimics of the human phenotype, being much less severe, and it is not certain if these findings can be generalized (6). In humans with dysferlinopathy, pathological differences depending on exercise type or intensity have not been assessed and it is not clear if early influences of exercise would remain detectable after many years of symptomatic disease.…”