Isometric resistance training increases strength and alters histopathology of dystrophin-deficient mouse skeletal muscle

Angus Lindsay, Alexie A. Larson, Mayank Verma, James M Ervasti, Dawn A Lowe

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Mutation to the dystrophin gene causes skeletal muscle weakness in patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD). Deliberation continues regarding implications of prescribing exercise for these patients. The purpose of this study was to determine whether isometric resistance exercise (~10 tetanic contractions/session) improves skeletal muscle strength and histopathology in the mdx mouse model of DMD. Three isometric training sessions increased in vivo isometric torque (22%) and contractility rates (54%) of anterior crural muscles of mdx mice. Mice expressing a BMD-causing missense mutated dystrophin on the mdx background showed comparable increases in torque (22%), while wild-type mice showed less change (11%). Increases in muscle function occurred within 1 h and peaked 3 days posttraining; however, the adaptation was lost after 7 days unless retrained. Six isometric training sessions over 4 wk caused increased isometric torque (28%) and contractility rates (22–28%), reduced fibrosis, as well as greater uniformity of fiber cross-sectional areas, fewer embryonic myosin heavy-chain-positive fibers, and more satellite cells in tibialis anterior muscle compared with the contralateral untrained muscle. Ex vivo functional analysis of isolated extensor digitorum longus (EDL) muscle from the trained hindlimb revealed greater absolute isometric force, lower passive stiffness, and a lower susceptibility to eccentric contraction-induced force loss compared with untrained EDL muscle. Overall, these data support the concept that exercise training in the form of isometric tetanic contractions can improve contractile function of dystrophin-deficient muscle, indicating a potential role for enhancing muscle strength in patients with DMD and BMD.

Original languageEnglish (US)
Pages (from-to)363-375
Number of pages13
JournalJournal of applied physiology
Volume126
Issue number2
DOIs
StatePublished - Feb 2019

Keywords

  • Becker muscular dystrophy
  • Duchenne muscular dystrophy
  • Exercise
  • Satellite cells
  • Skeletal muscle

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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