Axonal sprouting in mdx mice and its relevance to cell and gene mediated therapies for Duchenne muscular dystrophy.
We investigated whether pre-terminal axons and motor terminals retained their ability to sprout in the murine X-linked muscular dystrophy (mdx). Immunofluorescence confocal microscopy observation of nerve terminals and acetylcholine receptors in mdx muscles with crushed and non-crushed nerves showed that most of the junctions had intraterminal sprouting and that the number of junctions with extraterminal sprouting increased after the nerve crush lesion. Since new dystrophin-positive muscle fibers generated by cell-mediated therapies need to be innervated to proceed with their maturation and dystrophin production, these results suggest that the use of inducing factors to increase the sprouting capacity of nerve terminals could be an additional tool in the success of cell-mediated therapies.
Santo Neto
Humberto
H
Departamento de Anatomia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, Campinas, 13084-971 São Paulo, Brazil.
Martins
Airton José
AJ
Minatel
Elaine
E
Marques
Maria Julia
MJ
D000818:Animals; D001369:Axons / Q000473:pathology* / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018613:Microscopy, Confocal / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy; D009334:Neck Muscles / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D009409:Nerve Crush; D009416:Nerve Regeneration; D009469:Neuromuscular Junction / Q000254:growth & development / Q000473:pathology; D012016:Reference Values