Properties of slow- and fast-twitch muscle fibres in a mouse model of amyotrophic lateral sclerosis

Neuromuscul Disord. 2005 May;15(5):377-88. doi: 10.1016/j.nmd.2005.02.005.

Abstract

This investigation was undertaken to determine if there are altered histological, pathological and contractile properties in presymptomatic or endstage diseased muscle fibres from representative slow-twitch and fast-twitch muscles of SOD1 G93A mice in comparison to wildtype mice. In presymptomatic SOD1 G93A mice, there was no detectable peripheral dysfunction, providing evidence that muscle pathology is secondary to motor neuronal dysfunction. At disease endstage however, single muscle fibre contractile analysis demonstrated that fast-twitch muscle fibres and neuromuscular junctions are preferentially affected by amyotrophic lateral sclerosis-induced denervation, being unable to produce the same levels of force when activated by calcium as muscle fibres from their age-matched controls. The levels of transgenic SOD1 expression, aggregation state and activity were also examined in these muscles but there no was no preference for muscle fibre type. Hence, there is no simple correlation between SOD1 protein expression/activity, and muscle fibre type vulnerability in SOD1 G93A mice.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases
  • Age Factors
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Animals
  • Blotting, Western / methods
  • Calcium / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / genetics
  • Humans
  • In Vitro Techniques
  • Mice
  • Mice, Transgenic
  • Muscle Fibers, Fast-Twitch / drug effects
  • Muscle Fibers, Fast-Twitch / metabolism
  • Muscle Fibers, Fast-Twitch / pathology
  • Muscle Fibers, Fast-Twitch / physiology*
  • Muscle Fibers, Slow-Twitch / drug effects
  • Muscle Fibers, Slow-Twitch / metabolism
  • Muscle Fibers, Slow-Twitch / pathology
  • Muscle Fibers, Slow-Twitch / physiology*
  • Strontium / pharmacology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Sympathectomy / methods

Substances

  • SOD1 protein, human
  • SOD1 G93A protein
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Adenosine Triphosphatases
  • Calcium
  • Strontium