Résumé :
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INTRODUCTION Myotonic dystrophy (DM1) is caused by abnormal expansion of a polymorphic (CTG)n repeat, located in the DM protein kinase gene. Respiratory problems are a major feature of DM1 and a main factor contributing to mortality. OBJECTIFS Since several pulmonary impairments are associated with phrenic nerve and diaphragm dysfunction, we examined the diaphragm and the respiratory neural network in a reliable animal model of human myotonic dystrophy disease. MÉTHODES Morphological and morphometric analysis of the diaphragm end-plates was made adjacent muscle sections labeled with rhodamine-conjugated a-bungarotoxin and neurofilament antibody. The medullary respiratory centers an the cervical spinal cord motor neurons were examined on frozen sections stained with toluidine blue. Semi-and ultra-thin sections of phrenic nerves were studied using light an electron microscopy. RÉSULTATS The diaphragm end-plates had significantly smaller size and less complex shapes in DM1 mice than in control and the mean density of ACh receptors on the postsynaptic membrane was decreased in DM1 mice. At the level of phrenic nerves, there was a severe and significant decrease in the number of unmyelinated fibers in DM1 mice, but, no loss of myelinated fibers was found. Also no pathological signs or loss in neuronal cells were detected either in the medullary respiratory centers or in cervical spinal cord motor neurons. DISCUSSION The absence of loss in the number of myelinated fibers in the middle trunk of phrenic nerve indicates that the generation of the breathing rhythm is likely not affected in DM-1 mice and the denervation of end-plates is due to distal or intramuscular nerve degeneration. This fact is also supported by the alterations in the structure of diaphragmatic NMJs and the reduction in the number of afferent phrenic unmyelinated fibers. CONCLUSION In conclusion, our results suggest that the respiratory impairment associated with myotonic dystrophy disease could be partially due to the pathological modifications in neuromuscular junctions and phrenic nerves.
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