From the Department of Molecular Biology, Hospital La Princesa, Madrid (RM-H); and Department of Genetics, IIB Sant Pau Research Institute, Hospital de Sant Pau and Centro de Investigación Biomédica en Red de Enfermedades Raras (SB, LA); and Department of Clinical and Molecular Genetics, Hospital Valle Hebron, Passeig Valle Hebron (EFT), Barcelona, Spain.
J Neuropathol Exp Neurol. 2014 Jun;73(6):559-67. doi: 10.1097/NEN.0000000000000078.
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.
脊髓性肌萎缩症（SMA）的特征是脊髓运动神经元的丧失，导致肌肉失神经支配和受影响患者的严重肌无力。我们通过分析 5 例 SMA 病例和 6 例对照的胎儿或出生后骨骼肌样本中几种肌细胞骨架成分（即慢肌、快肌和发育肌球蛋白、结蛋白和波形蛋白）的表达，来寻找疾病在人类发育过程中主要累及肌肉的证据。在 14 周的胎龄时，与对照样本相比，SMA 样本中表达快肌球蛋白的肌管比例更高，而表达慢肌球蛋白的肌管比例更低。在产前阶段，结蛋白和波形蛋白表达水平较高，在对照和 SMA 样本之间没有明显差异，尽管这两种蛋白在出生后的 SMA 样本中萎缩纤维中均持续免疫染色。我们还研究了 Pax7 阳性核作为卫星细胞的标志物的表达，未发现对照和 SMA 产前样本之间有差异。然而，在出生后的萎缩性 SMA 纤维中，卫星细胞显著增加，表明存在异常的肌生成过程。这些结果共同支持了肌肉成熟延迟是 SMA 的主要病理成分之一的假说。此外，肌球蛋白和 Pax7 可能是该疾病肌肉受累的有用研究标志物。
