Résumé :
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Communication n° 300 Amyotrophic Lateral Sclerosis (ALS) is the most frequent fatal motoneuron disease. Degeneration of the motoneurons causes a progressive paralysis of the limbs, an amyotrophy and respiratory insufficiency, which is the main cause of death. However, biochemical deregulation within the ALS skeletal muscle could be involved, at least partly, in the degeneration of motoneurons. Recently, modifications in gene expression in both lumbar spinal cord and skeletal muscle of ALS patients were described. Among these genes, Nogo-A, an inhibitor of axonal growth, was found to be over-expressed in ALS skeletal muscle. The aim of this study is to investigate whether skeletal muscle could contribute to the onset of the ALS phenotype and to the motoneuron degeneration. We have established and characterized myoblast cultures from an ALS patient with a sporadic form. The proliferative capacity of ALS myoblasts does not differ from age-matched controls, although most of the cells present a senescent or stressed morphology (large and flattened). However, no changes in the activities of the complexes II, III and IV of the mitochondrial respiratory chain and the citrate synthase were found in the ALS muscle cells when compared to age-matched control cells. When switched to differentiation medium, ALS myoblasts fuse and form myotubes expressing the various MyHCs. However, the expression of the fast- and slow-MyHC is weaker when compared to control myotubes. We are currently establishing conditions for co-culture between mouse spinal cord cells and either ALS myoblasts or myoblasts over-expressing Nogo-A.
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