Résumé :
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Communication n° 673 INTRODUCTION : We demonstrated that Nogo isoforms (Nogo-A, Nogo-B, Nogo-C) exhibit a specific pattern of expression in the skeletal muscle of mutant Cu/Zn-superoxide dismutase (SOD1G86R) transgenic mice and patients with sporadic amyotrophic lateral sclerosis (ALS). OBJECTIVE : In this study, we analysed whether changes observed in Nogo expression correlate with motor dysfunction in ALS. To this aim, we compared the expression levels of Nogo proteins in muscle biopsies with both the severity of motor impairment as measured by the ALS functional rating scale and the degree of muscular atrophy. METHODS : Muscle biopsies were obtained from 15 patients with clinically probable or definite ALS. Serial sections were cut perpendicular to the muscle axis on a cryostat and muscle fibres were classified according to their contractile speed using myofibril ATPase histochemistry. The area of fibres was measured using Lucia G version 4,61 software for image analysis. For immunohistochemistry studies, sections were immunostained using the avidin-biotin-peroxydase method. Contents of Nogo proteins in muscle extracts were analyzed by Western blot. Comparisons between Nogo protein expressions, ALS-FRS, fibres area, and other characteristics were accomplished using non-parametric Spearman correlation test. RESULTS : Expression levels of Nogo-A and Nogo-B tended to increase together and these changes correlated with both ALS FRS and with the mean area of slow-twitch type I fibres. Nogo-C expression levels correlated with the mean area of fast-twitch type II fibres. No correlation was observed with age or the duration of the disease. In addition, Nogo-A immunoreactivity was selectively expressed by atrophic slow-twitch type I fibres. CONCLUSION Our findings strongly suggest that amounts of Nogo-A and Nogo-B proteins vary according to the motor disabilities, which are presumably related to the number of motor neurons innervating the skeletal muscle. Thus, the expression of these proteins could provide a potential marker of disease progression.
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