TY - JOUR
T1 - Skeletal muscle weakness due to deficiency of CuZn-superoxide dismutase is associated with loss of functional innervation
AU - Larkin, Lisa M.
AU - Davis, Carol S.
AU - Sims-Robinson, Catrina
AU - Kostrominova, Tatiana Y.
AU - van Remmen, Holly
AU - Richardson, Arlan
AU - Feldman, Eva L.
AU - Brooks, Susan V.
PY - 2011/11
Y1 - 2011/11
N2 - 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 dismutasedeficient (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.
AB - 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 dismutasedeficient (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.
KW - Denervation
KW - Sod1
KW - Specific force
UR - http://www.scopus.com/inward/record.url?scp=80155165243&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80155165243&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00093.2011
DO - 10.1152/ajpregu.00093.2011
M3 - Article
C2 - 21900648
AN - SCOPUS:80155165243
VL - 301
SP - R1400-R1407
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 5
ER -