title: The role of oxidative stress in nervous system aging.
abstract: While oxidative stress is implicated in aging, the impact of oxidative stress on aging in the peripheral nervous system is not well understood. To determine a potential mechanism for age-related deficits in the peripheral nervous system, we examined both functional and morphological changes and utilized microarray technology to compare normal aging in wild-type mice to effects in copper/zinc superoxide dismutase-deficient (Sod1(-/-)) mice, a mouse model of increased oxidative stress. Sod1(-/-) mice exhibit a peripheral neuropathy phenotype with normal sensory nerve function and deficits in motor nerve function. Our data indicate that a decrease in the synthesis of cholesterol, which is vital to myelin formation, correlates with the structural deficits in axons, myelin, and the cell body of motor neurons in the Sod1(+/+) mice at 30 months and the Sod1(-/-) mice at 20 months compared with mice at 2 months. Collectively, we have demonstrated that the functional and morphological changes within the peripheral nervous system in our model of increased oxidative stress are manifested earlier and resemble the deficits observed during normal aging.
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Catrina
authors.initials: C
authors.lastname: Sims-Robinson
authors.forename: Junguk
authors.initials: J
authors.lastname: Hur
authors.forename: John M
authors.initials: JM
authors.lastname: Hayes
authors.forename: Jacqueline R
authors.initials: JR
authors.lastname: Dauch
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Keller
authors.forename: Susan V
authors.initials: SV
authors.lastname: Brooks
authors.forename: Eva L
authors.initials: EL
authors.lastname: Feldman
mesh_terms: D000375:Aging; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D002784:Cholesterol / Q000096:biosynthesis; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009046:Motor Neurons / Q000378:metabolism / Q000648:ultrastructure; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure; D009420:Nervous System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009431:Neural Conduction / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D013997:Time Factors
chemical_list: C000606290:SOD1 protein, human; D002784:Cholesterol; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1