title: Skeletal muscle weakness due to deficiency of CuZn-superoxide dismutase is associated with loss of functional innervation.
abstract: An association between oxidative stress and muscle atrophy and weakness in vivo is supported by elevated oxidative damage and accelerated loss of muscle mass and force with aging in CuZn-superoxide dismutase-deficient (Sod1(-/-)) mice. The purpose was to determine the basis for low specific force (N/cm(2)) of gastrocnemius muscles in Sod1(-/-) mice and establish the extent to which structural and functional changes in muscles of Sod1(-/-) mice resemble those associated with normal aging. We tested the hypothesis that muscle weakness in Sod1(-/-) mice is due to functionally denervated fibers by comparing forces during nerve and direct muscle stimulation. No differences were observed for wild-type mice at any age in the forces generated in response to nerve and muscle stimulation. Nerve- and muscle-stimulated forces were also not different for 4-wk-old Sod1(-/-) mice, whereas, for 8- and 20-mo-old mice, forces during muscle stimulation were 16 and 30% greater, respectively, than those obtained using nerve stimulation. In addition to functional evidence of denervation with aging, fiber number was not different for Sod1(-/-) and wild-type mice at 4 wk, but 50% lower for Sod1(-/-) mice by 20 mo, and denervated motor end plates were prevalent in Sod1(-/-) mice at both 8 and 20 mo and in WT mice by 28 mo. The data suggest ongoing denervation in muscles of Sod1(-/-) mice that results in fiber loss and muscle atrophy. Moreover, the findings support using Sod1(-/-) mice to explore mechanistic links between oxidative stress and the progression of deficits in muscle structure and function.
authors: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109-2200, USA.
authors: Lisa M
authors: LM
authors: Larkin
authors: Carol S
authors: CS
authors: Davis
authors: Catrina
authors: C
authors: Sims-Robinson
authors: Tatiana Y
authors: TY
authors: Kostrominova
authors: Holly
authors: H
authors: Van Remmen
authors: Arlan
authors: A
authors: Richardson
authors: Eva L
authors: EL
authors: Feldman
authors: Susan V
authors: SV
authors: Brooks
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism; D000818:Animals; D004558:Electric Stimulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000201:enzymology* / Q000473:pathology; D053580:Muscle Strength; D018908:Muscle Weakness; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000294:innervation* / Q000473:pathology; D009133:Muscular Atrophy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1