Improvement of Dystrophic Muscle Fragility by Short-Term Voluntary Exercise through Activation of Calcineurin Pathway in mdx Mice - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue American Journal of Pathology Année : 2018

Improvement of Dystrophic Muscle Fragility by Short-Term Voluntary Exercise through Activation of Calcineurin Pathway in mdx Mice

Clement Delacroix
  • Fonction : Auteur
Megane Lemaitre
  • Fonction : Auteur
Bertrand Friguet
  • Fonction : Auteur
Zhenlin Li
  • Fonction : Auteur
Arnaud Klein
  • Fonction : Auteur
Onnik Agbulut
  • Fonction : Auteur
Arnaud Ferry
  • Fonction : Auteur

Résumé

Dystrophin deficiency in mdx mice, a model for Duchenne muscular dystrophy, leads to muscle weakness revealed by a reduced specific maximal force as well as fragility (ie, higher susceptibility to contraction-induced injury, as shown by a greater force decrease after lengthening contractions). Both symptoms could be improved with dystrophin restoration-based therapies and long-term (months) voluntary exercise. Herein, we evaluated the effect of short-term (1-week) voluntary wheel running. We found that running improved fragility of tibialis anterior muscle (TA), but not plantaris muscle, independently of utrophin up-regulation, without affecting weakness. Moreover, TA muscle excitability was also preserved by running, as shown by compound muscle action potential measurements after lengthening contractions. Of interest, the calcineurin inhibitor cyclosporin A prevented the effect of running on both muscle fragility and excitability. Cyclosporin also prevented the running-induced changes in expression of genes involved in excitability (Scn4a and Cacna1s) and slower contractile phenotype (Myh2 and Tnni1) in TA muscle. In conclusion, short-term voluntary exercise improves TA muscle fragility in mdx mice, without worsening weakness. Its effect was related to preserved excitability, calcineurin pathway activation, and changes in the program of genes involved in excitability and slower contractile phenotype. Thus, remediation of muscle fragility of Duchenne muscular dystrophy patients through appropriate exercise training deserves to be explored in more detail.

Dates et versions

hal-04443109 , version 1 (07-02-2024)

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Citer

Clement Delacroix, Janek Hyzewicz, Megane Lemaitre, Bertrand Friguet, Zhenlin Li, et al.. Improvement of Dystrophic Muscle Fragility by Short-Term Voluntary Exercise through Activation of Calcineurin Pathway in mdx Mice. American Journal of Pathology, 2018, 188 (11), pp.2662-2673. ⟨10.1016/j.ajpath.2018.07.015⟩. ⟨hal-04443109⟩
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