Selective vulnerability in neuronal populations in nmd/SMARD1 mice.
Hum Mol Genet
; 27(4): 679-690, 2018 02 15.
Article
em En
| MEDLINE
| ID: mdl-29272405
ABSTRACT
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an autosomal recessive motor neuron disease causing distal limb muscle atrophy that progresses proximally and is accompanied by diaphragmatic paralysis. Neuromuscular junction (NMJ) alterations have been reported in muscles of SMARD1 model mice, known as nmd mice, with varying degrees of severity, suggesting that different muscles are specifically and selectively resistant or susceptible to denervation. To evaluate the extent of NMJ pathology in a broad range of muscles, a panel of axial and appendicular muscles were isolated and immunostained from nmd mice. These analyses revealed that selective distal appendage muscles were highly vulnerable to denervation. Susceptibility to pathology was not limited to NMJ alterations, but included defects in myelination within those neurons innervating susceptible muscles. Interestingly, end plate fragmentation was present within all muscles independent of the extent of NMJ alterations, suggesting that end plate fragmentation is an early hallmark of SMARD1 pathogenesis. Expressing the full-length IGHMBP2 cDNA using an adeno-associated virus (AAV9) significantly decreased all aspects of muscle and nerve disease pathology. These results shed new light onto the pathogenesis of SMARD1 by identifying specific motor units that are resistant and susceptible to neurodegeneration in an important model of SMARD1.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome do Desconforto Respiratório do Recém-Nascido
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Atrofia Muscular Espinal
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Músculo Esquelético
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Junção Neuromuscular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Hum Mol Genet
Ano de publicação:
2018
Tipo de documento:
Article