Muscle contractility dysfunction precedes loss of motor unit connectivity in SOD1(G93A) mice

Muscle Nerve. 2019 Feb;59(2):254-262. doi: 10.1002/mus.26365. Epub 2018 Dec 21.

Abstract

Introduction: Electrophysiological measurements are used in longitudinal clinical studies to provide insight into the progression of amyotrophic lateral sclerosis (ALS) and the relationship between muscle weakness and motor unit (MU) degeneration. Here, we used a similar longitudinal approach in the Cu/Zn superoxide dismutase (SOD1[G93A]) mouse model of ALS.

Methods: In vivo muscle contractility and MU connectivity assays were assessed longitudinally in SOD1(G93A) and wild type mice from postnatal days 35 to 119.

Results: In SOD1(G93A) males, muscle contractility was reduced by day 35 and preceded MU loss. Muscle contractility and motor unit reduction were delayed in SOD1(G93A) females compared with males, but, just as with males, muscle contractility reduction preceded MU loss.

Discussion: The longitudinal contractility and connectivity paradigm employed here provides additional insight into the SOD1(G93A) mouse model and suggests that loss of muscle contractility is an early finding that may precede loss of MUs and motor neuron death. Muscle Nerve 59:254-262, 2019.

Keywords: ALS; connectivity; contractility; electrophysiology; motor unit.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / genetics
  • Age Factors
  • Amyotrophic Lateral Sclerosis / complications
  • Amyotrophic Lateral Sclerosis / genetics
  • Animals
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Longitudinal Studies
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Neurons / physiology*
  • Muscle Contraction / genetics*
  • Muscle Contraction / physiology
  • Muscle, Skeletal / physiopathology*
  • Muscular Diseases / etiology
  • Muscular Diseases / physiopathology*
  • Neuromuscular Junction / diagnostic imaging
  • Neuromuscular Junction / genetics
  • Superoxide Dismutase / genetics
  • Torque

Substances

  • SOD1 G93A protein
  • Superoxide Dismutase