Progressive abnormalities in skeletal muscle and neuromuscular junctions of transgenic mice expressing the Huntington's disease mutation

摘要: Huntington's disease (HD) is a neurodegenerative disorder with complex symptoms dominated by progressive motor dysfunction. Skeletal muscle atrophy common in HD patients. Because the mutation expressed skeletal as well brain, we wondered whether changes arise from primary pathology. We used R6/2 transgenic mice for our studies. Unlike denervation atrophy, occurs uniformly. Paradoxically however, muscles show age-dependent denervation-like abnormalities, including supersensitivity to acetylcholine, decreased sensitivity mu-conotoxin, and anode-break action potentials. Morphological abnormalities of neuromuscular junctions are also present, particularly older mice. Severely affected increase number endplates that fail respond nerve stimulation. Surprisingly, there was no constitutive sprouting neurons muscles, even severely atrophic showed other characteristics. In fact, an loss regenerative capacity fibers appear be released activity-dependent cues regulate membrane properties size, axons terminals become impaired their release neurotransmitter stimuli normally evoke adaptive reinnervation, speculate these dissociation trophic signalling between muscle. However, irrespective cause, at report here likely contribute pathological phenotype mice, late stages disease.