View More View Less
  • 1 Universidade Estadual de Campinas (UNICAMP) Departmento de Anatomia, Instituto de Biologia Campinas, São Paulo 13083-970 Brazil
Restricted access

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 dystrophic 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.

  • Balice-Gordon, R. J., Lichtman, J. W. (1993) In vivo observations of pre- and postsynaptic changes during the transition from multiple to single innervation at developing neuromuscular junctions. J. Neurosci. 1 , 834–855.

    Lichtman J. W. , 'In vivo observations of pre- and postsynaptic changes during the transition from multiple to single innervation at developing neuromuscular junctions ' (1993 ) 1 J. Neurosci. : 834 -855.

    • Search Google Scholar
  • Bertorini, T. E., Bhattacharya, S. K., Palmieri, G. M. M. A., Chesney, C. M., Pifer, D., Baker, B. (1982) Muscle calcium and magnesium content in Duchenne muscular dystrophy. Neurology 32 , 1088–1092.

    Baker B. , 'Muscle calcium and magnesium content in Duchenne muscular dystrophy ' (1982 ) 32 Neurology : 1088 -1092.

    • Search Google Scholar
  • Brenman, J. E., Chao, D. S., Xia, H., Aldape, K., Bredt, D. S. (1995) Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell 82 , 743–752.

    Bredt D. S. , 'Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy ' (1995 ) 82 Cell : 743 -752.

    • Search Google Scholar
  • Brussee, V., Tardif, F., Tremblay, J. P. (1997) Muscle fibers of mdx mice are more vulnerable to exercise than those of normal mice. Neuromusc. Disord. 7 , 487–492.

    Tremblay J. P. , 'Muscle fibers of mdx mice are more vulnerable to exercise than those of normal mice ' (1997 ) 7 Neuromusc. Disord. : 487 -492.

    • Search Google Scholar
  • Grounds, M. D. (2002) Reasons for the degeneration of ageing skeletal muscle: a central role for IGF-1 signalling. Biogerontology 3 , 19–24.

    Grounds M. D. , 'Reasons for the degeneration of ageing skeletal muscle: a central role for IGF-1 signalling ' (2002 ) 3 Biogerontology : 19 -24.

    • Search Google Scholar
  • Hamer, P. W., McGeachie, J. M., Davies, M. J., Grounds, M. D. (2002) Evans blue dye an in vivo marker of myofibre damage: optimising parameters for detecting initial myofibre membrane permeability. J. Anat. 200 , 69–79.

    Grounds M. D. , 'Evans blue dye an in vivo marker of myofibre damage: optimising parameters for detecting initial myofibre membrane permeability ' (2002 ) 200 J. Anat. : 69 -79.

    • Search Google Scholar
  • Matsuda, R. A., Nishikawa, A., Tanaka, H. (1995) Vizualization of dystrophic muscle fibers in mdx mouse by vital staining with Evans blue: evidence of apoptosis in dystrophin-deficient muscle. J. Biochem. 118 , 959–964.

    Tanaka H. , 'Vizualization of dystrophic muscle fibers in mdx mouse by vital staining with Evans blue: evidence of apoptosis in dystrophin-deficient muscle ' (1995 ) 118 J. Biochem. : 959 -964.

    • Search Google Scholar
  • Minatel, E., Santo Neto, H., Marques, M. J. (2003) Acetylcholine receptor distribution and synapse elimination at the developing neuromuscular junction of mdx mice. Muscle Nerve 2 , 561–569.

    Marques M. J. , 'Acetylcholine receptor distribution and synapse elimination at the developing neuromuscular junction of mdx mice ' (2003 ) 2 Muscle Nerve : 561 -569.

    • Search Google Scholar
  • Mokhtarian, A., Lefaucheur, J. P., Even, P. C., Sebille, A. (1995) Effects of treadmill exercise and high-fat feeding on muscle degeneration in mdx mice at the time of weaning. Clin. Sci. 89 , 447–452.

    Sebille A. , 'Effects of treadmill exercise and high-fat feeding on muscle degeneration in mdx mice at the time of weaning ' (1995 ) 89 Clin. Sci. : 447 -452.

    • Search Google Scholar
  • Pastoret, C., Sebille, A. (1993) Time-course study of the isometric contractile properties of mdx mouse striated muscles. J. Muscle Res. Cell M. 14 , 423–431.

    Sebille A. , 'Time-course study of the isometric contractile properties of mdx mouse striated muscles ' (1993 ) 14 J. Muscle Res. Cell M. : 423 -431.

    • Search Google Scholar
  • Pastoret, C., Sebille, A. (1995) mdx mice show progressive weakness and muscle deterioration with age. J. Neurol. Sci. 129 , 97–105.

    Sebille A. , 'mdx mice show progressive weakness and muscle deterioration with age ' (1995 ) 129 J. Neurol. Sci. : 97 -105.

    • Search Google Scholar
  • Pereira, E. C. L., Santo Neto, H., Marques, M. J. (2001) Immunolocalization of neuronal nitric oxide synthase at the neuromuscular junction of mdx mice: a confocal microscopy study. J. Anat. 198 , 663–671.

    Marques M. J. , 'Immunolocalization of neuronal nitric oxide synthase at the neuromuscular junction of mdx mice: a confocal microscopy study ' (2001 ) 198 J. Anat. : 663 -671.

    • Search Google Scholar
  • Personius, K. E., Sawyer, R. P. (2005) Terminal Schwann cell structure is altered in diaphragm of mdx mice. Muscle Nerve 32 , 656–663.

    Sawyer R. P. , 'Terminal Schwann cell structure is altered in diaphragm of mdx mice ' (2005 ) 32 Muscle Nerve : 656 -663.

    • Search Google Scholar
  • Porter, J. D., Baker, R. S., Ragusa, R. J., Brueckner, J. K. (1995) Extraocular muscles: basic and clinical aspects of structure and function. Surv. Ophthalmol. 39 , 451–484.

    Brueckner J. K. , 'Extraocular muscles: basic and clinical aspects of structure and function ' (1995 ) 39 Surv. Ophthalmol. : 451 -484.

    • Search Google Scholar
  • Sanes, J. R., Lichtman, J. W. (1999) Development of the vertebrate neuromuscular junction. Annu. Rev. Neurosci. 22 , 389–442.

    Lichtman J. W. , 'Development of the vertebrate neuromuscular junction ' (1999 ) 22 Annu. Rev. Neurosci. : 389 -442.

    • Search Google Scholar
  • Straub, V., Rafael, J. A., Chamberlain, J. S., Campbell, K. P. (1997) Animal models for muscular dystrophy show different patterns of sarcolema disruption. J. Cell Biol. 139 , 375–385.

    Campbell K. P. , 'Animal models for muscular dystrophy show different patterns of sarcolema disruption ' (1997 ) 139 J. Cell Biol. : 375 -385.

    • Search Google Scholar
  • Tanabe, Y., Esaki, K., Nomura, T. (1986) Skeletal muscle pathology in X chromosome-linked muscular dystrophy ( mdx ) mouse. Acta Neuropathol. 69 , 91–95.

    Nomura T. , 'Skeletal muscle pathology in X chromosome-linked muscular dystrophy (mdx) mouse ' (1986 ) 69 Acta Neuropathol. : 91 -95.

    • Search Google Scholar
  • Torres, L. F., Duchen, L. W. (1987) The mutant mdx: inherited myopathy in the mouse. Morphological studies of nerves, muscle and end-plates. Brain 110 , 269–299.

    Duchen L. W. , 'The mutant mdx: inherited myopathy in the mouse. Morphological studies of nerves, muscle and end-plates ' (1987 ) 110 Brain : 269 -299.

    • Search Google Scholar
  • Vandebrouck, A., Ducret, T., Basset, O., Sebille, S., Raymond, G., Ruegg, U., Gailly, P., Cognard, C., Constantin, B. (2006) Regulation of store-operated calcium entries and mitochondrial uptake by minidystrophin expression in culture myotubes. FASEB J. 20 , 36–138.

    Constantin B. , 'Regulation of store-operated calcium entries and mitochondrial uptake by minidystrophin expression in culture myotubes ' (2006 ) 20 FASEB J. : 36 -138.

    • Search Google Scholar
  • Zhang, N., Beuve, A., Townes-Anderson, E. (2005) The nitric oxide-cGMP signaling pathway differentially regulates presynaptic structural plasticity in cone and rod cells. J. Neurosci. 25 , 2761–2770.

    Townes-Anderson E. , 'The nitric oxide-cGMP signaling pathway differentially regulates presynaptic structural plasticity in cone and rod cells ' (2005 ) 25 J. Neurosci. : 2761 -2770.

    • Search Google Scholar