Résumé :
|
Objective: Myotonic dystrophy (DM1, also known as Steinert disease) is characterized primarily by myotonia and muscle weakness and is a multisystemic disorder. Although several studies have been carried out to verify the possible involvement of the peripheral nervous system in DM1, the results have not been univocal and at present, the possible association between peripheral neuropathy and DM1 remains open. Our present study was designed to investigate the presence/absence and the possible type of peripheral neuropathy in a reliable DM1 animal model.Methods: Recently, new transgeinc mice (DMSXL) carrying > 1,300 CTGs and displaying severe DM1 features were generated. To investigate whether DMSXL mice show peripheral neuropathy, we measured the evoked compound muscle action potential (CMAP) in gastrocnemius muscles and the nerve conduction velocity (NCV) of the sciatic nerves in control and DMSXL mice. We also estimated the number of motor neurons in lumbar spinal cord segments (L4 and L5) by the physical dissector method. The structure of the sciatic nerve and the neuromuscular junctions (NMJs) on gastrocnemius muscle sections labelled with alpha-bungarotoxin and neurofilament antibody were carefully analyzed.Results: Electrophysiological data recorded from control and DMSXL mice revealed that every DMSXL mouse examined exhibited electrophysiological abnormalities compared to control mice. These abnormalities consisted of a significant decrease in both CMAP parameters and NCV. This result indicates the dysfunction of muscles and peripheral nerves in DMSXL mice compared to control mice. Histological and morphometric analysis showed an axonopathy and neuronopathy in DMSXL mice, characterized by a significant decrease in the number of myelinated motor axons in the sciatic nerve and in motor neurons in lumbar spinal cord region. Also, pathological changes in the size and shape complexity of hind limb end-plates were detected in DMSXL mice. In addition a reduction in the density of acetylcholine receptors on post synaptic membranes was quantitated using the fluorescence intensity.Conclusion: We already shown that transgenic mice expressing the mild DM1 phenotype (carrying 350-500 CTG repeats) do not exhibit any sensory or motor neuropathy (Gantelet et al.2007), therefore the results of our previous and present studies lead us to infer that peripheral neuropathy is linked to a large CTG expansion and a severe form of DM1. (This study is supported by AFM)
|