Mitochondrial changes in skeletal muscle in amyotrophic lateral sclerosis and other neurogenic atrophies

Brain. 2005 Aug;128(Pt 8):1870-6. doi: 10.1093/brain/awh540. Epub 2005 May 18.

Abstract

Previous findings suggested specific mitochondrial dysfunction in skeletal muscle of patients with amyotrophic lateral sclerosis (ALS). To answer the question of whether the dysfunction is specific, we investigated the histochemical distribution of mitochondrial marker activities, the ratio of mitochondrial (mt) versus nuclear (n) DNA, and the activities of citrate synthase (CS) and respiratory chain enzymes in muscle biopsies of 24 patients with sporadic ALS. The data were compared with those in 23 patients with other neurogenic atrophies (NAs), and 21 healthy controls. Muscle histology revealed similar signs of focally diminished mitochondrial oxidation activity in muscle fibres in both diseased groups. There was only minimal decline of mt/nDNA ratios in ALS and NA patients in comparison with healthy controls. The specific activities of mitochondrial markers CS and succinate dehydrogenase were significantly increased in both ALS and NA patients. The specific activities of respiratory chain enzymes were not significantly different in all three groups. It is concluded that the histochemical, biochemical and molecular mitochondrial changes in muscle are not specific for ALS, but accompany other NAs as well.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Biomarkers / analysis
  • Citrate (si)-Synthase / metabolism
  • DNA / analysis
  • DNA, Mitochondrial / analysis
  • Electron Transport
  • Electron Transport Complex IV / metabolism
  • Female
  • Glucose-6-Phosphate Isomerase / metabolism
  • Humans
  • Male
  • Middle Aged
  • Mitochondria, Muscle / chemistry*
  • Mitochondria, Muscle / genetics
  • Mitochondria, Muscle / metabolism
  • Multienzyme Complexes / metabolism
  • Muscle, Skeletal / chemistry*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / ultrastructure
  • Muscular Atrophy / genetics
  • Muscular Atrophy / metabolism
  • Succinate Dehydrogenase / metabolism

Substances

  • Biomarkers
  • DNA, Mitochondrial
  • Multienzyme Complexes
  • DNA
  • Succinate Dehydrogenase
  • Electron Transport Complex IV
  • Citrate (si)-Synthase
  • Glucose-6-Phosphate Isomerase