title: Incidence and severity of myofiber branching with regeneration and aging.
abstract: BACKGROUND
  Myofibers with an abnormal branching cytoarchitecture are commonly found in muscular dystrophy and in regenerated or aged nondystrophic muscles. Such branched myofibers from dystrophic mice are more susceptible to damage than unbranched myofibers in vitro, suggesting that muscles containing a high percentage of these myofibers are more prone to injury. Little is known about the regulation of myofiber branching.
  
  
  METHODS
  To gain insights into the formation and fate of branched myofibers, we performed in-depth analyses of single myofibers isolated from dystrophic and nondystrophic (myotoxin-injured or aged) mouse muscles. The proportion of branched myofibers, the number of branches per myofiber and the morphology of the branches were assessed.
  
  
  RESULTS
  Aged dystrophic mice exhibited the most severe myofiber branching as defined by the incidence of branched myofibers and the number of branches per myofiber, followed by myotoxin-injured, wild-type muscles and then aged wild-type muscles. In addition, the morphology of the branched myofibers differed among the various models. In response to either induced or ongoing muscle degeneration, branching was restricted to regenerated myofibers containing central nuclei. In myotoxin-injured muscles, the amount of branched myofibers remained stable over time.
  
  
  CONCLUSIONS
  We suggest that myofiber branching is a consequence of myofiber remodeling during muscle regeneration. Our present study lays valuable groundwork for identifying the molecular pathways leading to myofiber branching in dystrophy, trauma and aging. Decreasing myofiber branching in dystrophic patients may improve muscle resistance to mechanical stress.
authors.affiliation: Department of Pharmacology, Rollins Research Center, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pichavant
authors.affiliation: Department of Pharmacology, Rollins Research Center, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA.
authors.forename: Grace K
authors.initials: GK
authors.lastname: Pavlath
keywords: Aging; Muscle injury; Muscle regeneration; Muscular dystrophy; Myofiber branching; mdx