Alterations in The Permeability of Dystrophic Fibers During Neuromuscular Junction Development
In the mdx mice, lack of dystrophin leads to increases in calcium influx and myonecrosis, followed by muscle regeneration. Synapse elimination is faster in mdx than in controls, suggesting that increases in calcium influx during development could be involved. In the present study, we evaluated whether dys-trophic fibers display changes in permeability to Evans Blue Dye (EBD) during development of the neuromuscular junction. EBD is a sensitive label for the early detection of increased myofiber permeability and sarcolemmal damage. After intraperitoneal injection of EBD, sternomastoid (STN) and tibialis anterior (T. anterior) muscles were analyzed with fluorescence microscopy. At 01, 07 and 14 days of age, STN and TA mdx myofibers were not stained with EBD. At 21 days of age, positive labeling of TA and STN mdx myofibers was seen, suggesting permeability modification and myonecrosis. Adult muscles showed a decrease (T. anterior) or no changes (STN) in the amount of EBD-positive fibers. These results suggest that there is no sarcolemmal damage detected by EBD during development of dystrophic neuromuscular junctions and other factors may contribute to the earlier synapse elimination seen in dystrophic muscle.
Keywordscalcium regulation dystrophin Evans Blue mdx neuromuscular junction synapse elimination
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This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grants 95/6110-2, 01/00570-4 and 04/15526-9). H. S. N. and M. J. M. are recipients of fellowships from Conselho Nacional de Pesquisas (301286/03-5; 302880/04-6). C.Y.M was recipient of a fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant 02/08145-3).
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