title: Mitochondrial electron transport chain complex dysfunction in a transgenic mouse model for amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis is a fatal neurodegenerative disease that causes degeneration of motoneurons. Mutation of Cu,Zn superoxide dismutase (SOD1) is one cause for this disease. In mice, expression of mutant protein causes motoneuron degeneration and paralysis resembling the human disease. Morphological change, indicative of mitochondrial damage, occurs at early stages of the disease. To determine whether mitochondrial function changes during the course of disease progression, enzyme activities of mitochondrial electron transport chain in spinal cords from mice at different disease stages were measured using three different methods: spectrophotometric assay, in situ histochemical enzyme assay, and blue native gel electrophoresis combined with in-gel histochemical reaction. The enzyme activities were decreased in the spinal cord, particularly in the ventral horn, beginning at early disease stages. This decrease persisted throughout the course of disease progression. This decrease was not detected in the spinal cords of non-transgenic animals, of mice expressing the wild-type protein, and in cerebellum and dorsal horn of the spinal cords from mice expressing mutant protein. These results demonstrate a functional defect in mitochondria in the ventral horn region and support the view that mitochondrial damage plays a role in mutant SOD1-induced motoneuron degeneration pathway.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
authors.forename: Cheolwha
authors.initials: C
authors.lastname: Jung
authors.forename: Cynthia M J
authors.initials: CM
authors.lastname: Higgins
authors.forename: Zuoshang
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004579:Electron Transport; D042967:Electron Transport Complex I; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000032:analysis / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000032:analysis / Q000378:metabolism; D010088:Oxidoreductases / Q000032:analysis / Q000378:metabolism; D013053:Spectrophotometry; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013385:Succinate Dehydrogenase / Q000032:analysis / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D009097:Multienzyme Complexes; D010088:Oxidoreductases; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I