Terminal schwann cell distribution at the neuromuscular junction of the dystrophin-deficient MDX mice

The murine model of muscular dystrophy, the mdx mice, is widely used to study the pathogenesis of muscular dystrophies. These mice suffer an X-linked dystrophin deficiency and present cycles of muscle fiber degeneration-regeneration beginning at 21 days of age. At the present, we studied neuromuscular junction organization in the sternomastoid muscle of mdx mice, focusing on the distribution of terminal Schwann cells during early development and adults. Seven and 14 days after birth (n=200 endplates for each age), before the onset of muscle degeneration-regeneration, fluorescence confocal microscopy showed that there were no detectable differences in the pattern of Schwann cell distribution in the mdx compared to controls of the same age. Schwann cells had a diffuse pattern of distribution, covering the plaques of acetylcholine receptors. In adult mdx muscles, terminal Schwann cell processes filled the center of acetylcholine receptors islands, similar to nerve terminal distribution, at the majority of the junctions (n=200; 100%). Conversely, all of the adult control junctions (n=200) showed continuous processes of Schwann cells covering the continuous branches of acetylcholine receptors. These observations indicate that remodeling of the three components of the neuromuscular junction occurs only after the onset of the cycles of muscle fiber degeneration-regeneration, in the mdx mice.

An ultrastructural study of the temporal progress of neuromuscular junction regeneration after sciatic nerve transection and tubulization repair

The aim of this investigation was to study the timecourse of motor endplates in the extensor digitorum logus (EDL) muscle after peripheral nerve transection and tubulization repair. Adult male C57BL/6J mice received sciatic nerve transection at midhigh level and both proximal and distal nerve stumps were stured into a 5-mm long polyethylene tube to bridge a final nerve gap distance of 3mm. At 2 to 40 weeks postoperatively the EDL muscle on the operated side was fixed in situ and processed histochemically for visualization of cholinesterase-rich sites. Groups of muscle fibers containing motor endplates were then processed for electron microscopy (EM). Two weeks after tubulization the EDL muscle was entirely denervated: Schwann cells came into contact with the post-synaptic folds of the muscle fibers; there was an increase in concentration of collagen and fibroblasts at the synaptic sites. Reinnervation began 4 weeks after tube implantation, when the first axon terminals established contact with a small portion of the specialized subneural region, many synaptic folds were still covered by collagen fibers and, in some cases, Schwann cells remained interposed between the folds and the synaptic terminals. Twelve weeks after surgery all the neuromuscular junctions examined were reinnervated and looked normal; motor terminals were alawys located at the primary synaptic clefts, although rarely some subneural folds lacking nerve terminals were seen. At 12 to 40 weeks all motor endplates appeared normally innervated by EM criteria.