title: Neuron-specific expression of CuZnSOD prevents the loss of muscle mass and function that occurs in homozygous CuZnSOD-knockout mice.
abstract: Deletion of copper-zinc superoxide dismutase (CuZnSOD) in Sod1(-/-) mice leads to accelerated loss of muscle mass and force during aging, but the losses do not occur with muscle-specific deletion of CuZnSOD. To determine the role of motor neurons in the muscle decline, we generated transgenic Sod1(-/-) mice in which CuZnSOD was expressed under control of the synapsin 1 promoter (SynTgSod1(-/-) mice). SynTgSod1(-/-) mice expressed CuZnSOD in brain, spinal cord, and peripheral nerve, but not in other tissues. Sciatic nerve CuZnSOD content in SynTgSod1(-/-) mice was ~20% that of control mice, but no reduction in muscle mass or isometric force was observed in SynTgSod1(-/-) mice compared with control animals, whereas muscles of age-matched Sod1(-/-) mice displayed 30-40% reductions in mass and force. In addition, increased oxidative damage and adaptations in stress responses observed in muscles of Sod1(-/-) mice were absent in SynTgSod1(-/-) mice, and degeneration of neuromuscular junction (NMJ) structure and function occurred in Sod1(-/-) mice but not in SynTgSod1(-/-) mice. Our data demonstrate that specific CuZnSOD expression in neurons is sufficient to preserve NMJ and skeletal muscle structure and function in Sod1(-/-) mice and suggest that redox homeostasis in motor neurons plays a key role in initiating sarcopenia during aging.
authors.affiliation: 1University of Michigan, 2029 Biomedical Sciences Research Bldg., 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA. svbrooks@umich.edu.
authors.forename: Giorgos K
authors.initials: GK
authors.lastname: Sakellariou
authors.forename: Carol S
authors.initials: CS
authors.lastname: Davis
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Ivannikov
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Aphrodite
authors.initials: A
authors.lastname: Vasilaki
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Macleod
authors.forename: Arlan
authors.initials: A
authors.lastname: Richardson
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Jackson
authors.forename: Anne
authors.initials: A
authors.lastname: McArdle
authors.forename: Susan V
authors.initials: SV
authors.lastname: Brooks
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D004576:Electromyography; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000378:metabolism / Q000503:physiopathology; D009929:Organ Size / Q000235:genetics; D010084:Oxidation-Reduction; D055948:Sarcopenia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
chemical_list: C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: SOD1; heat-shock protein; neuromuscular junction; oxidative stress