Résumé :
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Dysferlinopathies are inherited myopathies characterized by a deficiency in dysferlin, a protein involved in plasma membrane repair process. Various clinical phenotypes/ modes of presentation are described, including LGMD2B, Myoshi-type distal myopathy, proximodistal onset, and hyperCKaemia, but no phenotype-genotype correlation has been identified so far. Moreover, most patients developed symptoms after a varying time period during which they were very active if not sportpersons, a feature usually not observed in other type of muscular dystrophies. Dysferlin-deficient mice A/J and B6.A/J-Dysfprmd have the same DYSF mutation but different genetic background. Compared to B6.A/J-Dysfprmd, A/J mice display less severe myopathy and reduced spontaneous locomotor activity. In B6.A/J-Dysfprmd and A/J mice, long-term eccentric exercise (forced running in engine-powered wheel, 30 min/d, 5 days/wk, 1 month) induced marked worsening of muscle injuries in parallel with muscle strength decrease. In contrast, long-term concentric exercise (swimming in adjustable-flow swimming-pool, 30 min/d, 5 days/wk, 1 month) had no deleterious effect and allowed training-induced improvement of muscle strength. By subjecting animals to a single bout of eccentric exercise we observed a delayed post-exercise myonecrosis, while concentric exercise did not. The delay was inversely proportional to the age of animal and electron microscopy examination showed that eccentric exercise-induced myonecrosis was preceded by an increase in sarcolemma disruptions. In conclusion (i) eccentric exercise may determine both the onset and the pattern of muscle injuries in dysferlinopathies; (ii) myofiber necrosis is determined by the accumulation of sarcolemmal disruption; and (iii) sustained concentric exercise may improve muscle strength. In a clinical context, the deleterious role of eccentric exercise and the potential benefits of concentric exercise should be of interest in the management of dysferlin-deficient patients.This work was supported by the AFM
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