Swim Training Modulates Mouse Skeletal Muscle Energy Metabolism and Ameliorates Reduction in Grip Strength in a Mouse Model of Amyotrophic Lateral Sclerosis

Int J Mol Sci. 2019 Jan 9;20(2):233. doi: 10.3390/ijms20020233.


Metabolic reprogramming in skeletal muscles in the human and animal models of amyotrophic lateral sclerosis (ALS) may be an important factor in the diseases progression. We hypothesized that swim training, a modulator of cellular metabolism via changes in muscle bioenergetics and oxidative stress, ameliorates the reduction in muscle strength in ALS mice. In this study, we used transgenic male mice with the G93A human SOD1 mutation B6SJL-Tg (SOD1G93A) 1Gur/J and wild type B6SJL (WT) mice. Mice were subjected to a grip strength test and isolated skeletal muscle mitochondria were used to perform high-resolution respirometry. Moreover, the activities of enzymes involved in the oxidative energy metabolism and total sulfhydryl groups (as an oxidative stress marker) were evaluated in skeletal muscle. ALS reduces muscle strength (-70% between 11 and 15 weeks, p < 0.05), modulates muscle metabolism through lowering citrate synthase (CS) (-30% vs. WT, p = 0.0007) and increasing cytochrome c oxidase and malate dehydrogenase activities, and elevates oxidative stress markers in skeletal muscle. Swim training slows the reduction in muscle strength (-5% between 11 and 15 weeks) and increases CS activity (+26% vs. ALS I, p = 0.0048). Our findings indicate that swim training is a modulator of skeletal muscle energy metabolism with concomitant improvement of skeletal muscle function in ALS mice.

Keywords: ALS; bioenergetics; exercise; mitochondria; neurodegeneration; oxidative stress.

MeSH terms

  • Amyotrophic Lateral Sclerosis / etiology
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Animals
  • Biomarkers
  • Disease Models, Animal
  • Electron Transport Complex IV / metabolism
  • Energy Metabolism*
  • Humans
  • Mice
  • Mice, Transgenic
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Muscle Strength*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / physiopathology
  • Oxidative Stress
  • Superoxide Dismutase-1 / genetics
  • Superoxide Dismutase-1 / metabolism
  • Swimming*


  • Biomarkers
  • Superoxide Dismutase-1
  • Electron Transport Complex IV