Résumé :
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Communication n° 665 INTRODUCTION : Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motoneurons localized in the spinal cord, brainstem and cortex. The first signs of paralysis appear when numerous motoneurons are lost, usually in adults of 50-70 years old. To date the initial mechanisms triggering the disease process and leading to the neurodegeneration are still unknown. AIM. Transgenic mouse models of ALS are very useful tools to study these early mechanisms. Recent studies on SOD1 models suggest that early abnormalities are already present during embryonic stage and postnatal period. Based on the hypothesis of early developmental changes, we recently studied the electrophysiological properties of spinal networks and motoneurons as well as the behaviour of SOD1-G85R mice (expressing the G85R mutant form of the human SOD1 allele) during post-natal period. METHOD : Using isolated brainstem/spinal cord in vitro preparations, we performed extracellular and intracellular recordings of lumbar ventral roots and motoneurons respectively, and the "Fox battery" was used to investigate the sensorimotor development of transgenics pups. RESULTS : SOD1-G85R transgenic mice displayed in vivo transient motor deficit (behavioural testing), and the electrophysiological recordings also revealed functional deficit concerning specifically the lumbar locomotor networks of SOD1-G85R mice compared to wild-type (WT) control mice. In contrast sacral segment are not concerned by these early alterations. Furthermore electrical properties of lumbar motoneurons (but not interneurons) differed between WT and transgenics pups. CONCLUSION : These results strongly support the fact that the G85R mutation may have altered the development of SOD1G85R transgenic mice. Compensatory mechanisms linked to developmental spinal plasticity might well developed explaining in part the late-onset of the disease. Identify precise mechanisms (alterations in ions conductances, motoneuron morphology and discharges properties, delayed maturation of supraspinal descending pathways) linked to these developmental changes may provide a valuable insight to understand the pathogenesis of ALS disease.
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