Abnormalities in Early Markers of Muscle Involvement Support a Delay in Myogenesis in Spinal Muscular Atrophy
Open Access
- 1 June 2014
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Neuropathology and Experimental Neurology
- Vol. 73 (6), 559-567
- https://doi.org/10.1097/nen.0000000000000078
Abstract
Spinal muscular atrophy (SMA) is characterized by loss of motor neurons in the spinal cord that results in muscle denervation and profound weakness in affected patients. We sought evidence for primary muscle involvement in the disease during human development by analyzing the expression of several muscle cytoskeletal components (i.e. slow, fast, and developmental myosin, desmin, and vimentin) in fetal or postnatal skeletal muscle samples from 5 SMA cases and 6 controls. At 14 weeks' gestation, SMA samples had higher percentages of myotubes expressing fast myosin and lower percentages of myotubes expressing slow myosin versus control samples. Desmin and vimentin were highly expressed at prenatal stages without notable differences between control and SMA samples, although both proteins showed persistent immunostaining in atrophic fibers in postnatal SMA samples. We also studied the expression of Pax7-positive nuclei as a marker of satellite cells and found no differences between control and SMA prenatal samples. There was, however, a significant increase in satellite cells in postnatal atrophic SMA fibers, suggesting an abnormal myogenic process. Together, these results support the hypothesis of a delay in muscle maturation as one of the primary pathologic components of SMA. Furthermore, myosins and Pax7 may be useful research markers of muscle involvement in this disease.Keywords
This publication has 35 references indexed in Scilit:
- Synaptic defects in type I spinal muscular atrophy in human developmentThe Journal of Pathology, 2012
- New insights into the pathogenesis of spinal muscular atrophyBrain & Development, 2011
- The Developmental Pattern of Myotubes in Spinal Muscular Atrophy Indicates Prenatal Delay of Muscle MaturationJournal of Neuropathology and Experimental Neurology, 2009
- Spinal muscular atrophy: DNA fragmentation and immaturity of muscle fibersActa Histochemica, 2008
- Constitutive muscular abnormalities in culture in spinal muscular atrophyThe Lancet, 1995
- Identification and characterization of a spinal muscular atrophy-determining geneCell, 1995
- International SMA Consortium Meeting (26–28 June 1992, Bonn, Germany)Neuromuscular Disorders, 1992
- Vimentin and desmin in maturing skeletal muscle and developmental myopathiesNeurology, 1992
- Evolution of muscle specific proteins in Werdnig-Hoffman's diseaseJournal of the Neurological Sciences, 1992
- Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy.Journal of Medical Genetics, 1978