title: No benefit of dietary restriction on disease onset or progression in amyotrophic lateral sclerosis Cu/Zn-superoxide dismutase mutant mice.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal disease in which spinal cord motor neurons degenerate resulting in progressive paralysis. Some cases of ALS are caused by mutations in the antioxidant enzyme Cu/Zn-superoxide dismutase (SOD). Transgenic mice expressing ALS-linked Cu/Zn-SOD mutations (SODMutM) exhibit a phenotype analogous to that of human ALS patients. Dietary restriction (DR) is a well-established means of extending lifespan in rodents. It may act by reducing levels of cellular oxidative stress. We therefore tested the hypothesis that DR will retard the development of the clinical phenotype and extend the lifespan of SODMutM. There was no significant difference in age of disease onset in mice placed on a DR regimen beginning at 6 weeks of age compared to mice fed ad libitum, and disease duration was shortened indicating that DR accelerates the clinical course. Histological analyses indicated a similar extent of lower motor neuron degeneration in SODMutM maintained on DR or ad libitum diets. We conclude that a dietary manipulation known to extend lifespan has no beneficial effect in an animal model of familial ALS.
authors.affiliation: Sanders-Brown Research Center on Aging and Department of Anatomy and Neurobiology, University of Kentucky, 211 Sanders-Brown Building, 800 South Limestone Street, Lexington, KY 40536, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: Pedersen
authors.forename: M P
authors.initials: MP
authors.lastname: Mattson
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000178:diet therapy* / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D018450:Disease Progression; D006801:Humans; D008136:Longevity; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic / Q000235:genetics; D009046:Motor Neurons / Q000473:pathology; D009154:Mutation / Q000502:physiology*; D010641:Phenotype; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D013482:Superoxide Dismutase