Dual effects of exercise in dysferlinopathy.

Abstract

Dysferlinopathy refers to a group of autosomal recessive muscular dystrophies due to mutations in the dysferlin gene causing deficiency of a membrane-bound protein crucially involved in plasma membrane repair. The condition is characterized by marked clinical heterogeneity, the different phenotypes/modes of presentation being unrelated to the genotype. For unknown reasons, patients are often remarkably active before the onset of symptoms. Dysferlin deficiency-related persistence of mechanically induced sarcolemma disruptions causes myofiber damage and necrosis. We postulate that limited myodamage may initially remain hidden with well-preserved resistance to physical strains. By subjecting dysferlin-deficient B6.A/J-Dysf(prmd) mice to long-term swimming exercise, we observed that concentric/isometric strain improved muscle strength and alleviated muscular dystrophy by limiting the accumulation of membrane lesions. By contrast, eccentric strain induced by long-term running in a wheel worsened the dystrophic process. Myofiber damage induced by eccentric strain increased with age, reflecting the accumulation of non-necrotic membrane lesions up to a critical threshold. This phenomenon was modulated by daily spontaneous activity. Transposed to humans, our results may suggest that the past activity profile shapes the clinical phenotype of the myopathy and that patients with dysferlinopathy should likely benefit from concentric exercise-based physiotherapy.

• Authors: Olivier Biondi, Marie Villemeur, Alice Marchand, Fabrice Chretien, Nathalie Bourg, Romain K Gherardi, Isabelle Richard, François-Jérôme Authier
• Journal: The American journal of pathology (Am J Pathol) Vol. 182 Issue 6 Pg. 2298-309 (Jun 2013) ISSN: 1525-2191 [Electronic] United States
• PMID: 23624156 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Dysf protein, mouse
• Dysferlin
• Membrane Proteins

Topics

• Aging (pathology, physiology)
• Animals
• Cell Membrane (ultrastructure)
• Dysferlin
• Locomotion (physiology)
• Membrane Proteins (deficiency)
• Mice
• Mice, Mutant Strains
• Microscopy, Electron
• Muscle Contraction (physiology)
• Muscle Fibers, Skeletal (pathology)
• Muscle Strength (physiology)
• Muscle, Skeletal (physiopathology)
• Muscular Dystrophies, Limb-Girdle (etiology, pathology, physiopathology, rehabilitation)
• Necrosis
• Physical Conditioning, Animal (physiology)
• Quadriceps Muscle (ultrastructure)
• Running (physiology)
• Swimming (physiology)