Résumé :
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Communication n° 68 ALS is caused by motor neuron loss in the spinal cord, although the mechanism(s) responsible are not known. Ubiquitous transgenic expression of familial ALS causing mutations in human copper/zinc superoxide dismutase (hSOD1mut) leads to an ALS phenotype in mice; however, restricted expression of hSOD1mut in neurons has no clinical consequences. Recently, Dupuis and colleagues (FASEB J. 2003 Nov;17(14):2091-3) reported UCP3 up-regulation in skeletal muscle, but not in spinal cord, from pre-clinical hSOD1(G86R) mice, and suggested that oxidative stress in skeletal muscle may be pathogenic in ALS. The purpose of the present investigation was to probe for oxidative stress and antioxidant enzyme adaptation in 95 d old hSOD1(G93A) skeletal muscle. We observed significant elevations in both malondialdehyde (27% and 29% in red and white gastrocnemius, respectively) and protein carbonyls (39% in red gastrocnemius) in hSOD1(G93A) mice. Copper/zinc SOD activity was higher in red and white hSOD1(G93A) gastrocnemius (7 and 10 fold, respectively), as was manganese SOD (4 and 5 fold, respectively) and catalase (2 and 2.5 fold, respectively). Eight weeks of endurance exercise training did not alter oxidative stress or antioxidant enzyme adaptations observed. Our data are the first to show oxidative stress and compensatory antioxidant enzyme up-regulation in skeletal muscle of hSOD1(G93A) mice. These findings support a model in which oxidative stress in skeletal muscle contributes to the pathogenesis of ALS.
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