Alexianu M E, Ho B K, Mohamed A H, La Bella V, Smith R G, Appel S H
Department of Neurology, Baylor College of Medicine, Houston, TX 77030.
Ann Neurol. 1994 Dec;36(6):846-58. doi: 10.1002/ana.410360608.
The factors contributing to selective motoneuron loss in amyotrophic lateral sclerosis (ALS) remain undefined. To investigate whether calcium-binding proteins contribute to selective motoneuron vulnerability in ALS, we compared calbindin-D28K and parvalbumin immunoreactivity in motoneuron populations in human ALS, and in a ventral spinal cord hybrid cell line selectively vulnerable to the cytotoxic effects of ALS IgG. In human autopsy specimens, immunoreactive calbindin-D28k and parvalbumin were absent in motoneuron populations lost early in ALS (i.e., cortical and spinal motoneurons, lower cranial nerve motoneurons), while motoneurons damaged late or infrequently in the disease (i.e., Onuf's nucleus motoneurons, oculomotor, trochlear, and abducens nerve neurons) expressed markedly higher levels of immunoreactive calbindin-D28K and/or parvalbumin. Motoneuron-neuroblastoma VSC 4.1 hybrid cells lost immunoreactive calbindin-D28k and parvalbumin following dibutyryl-cyclic AMP-induced differentiation and were killed by IgG from ALS patients. Undifferentiated calbindin/parvalbumin-reactive VSC 4.1 cells were not killed, nor were other cell lines expressing high levels of calbindin-D28K and parvalbumin immunoreactivity (substantia nigra-neuroblastoma hybrid cells and N18TG2 neuroblastoma parent cells). These studies suggest that decreased calbindin-D28K and parvalbumin immunoreactivity may help explain the selective vulnerability of motoneurons in ALS.
肌萎缩侧索硬化症（ALS）中导致选择性运动神经元丧失的因素仍不明确。为了研究钙结合蛋白是否导致ALS中运动神经元的选择性易损性，我们比较了人类ALS运动神经元群体以及选择性易受ALS IgG细胞毒性作用影响的腹侧脊髓杂交细胞系中钙结合蛋白-D28K和小白蛋白的免疫反应性。在人类尸检标本中，ALS早期丧失的运动神经元群体（即皮质和脊髓运动神经元、低位颅神经运动神经元）中不存在免疫反应性钙结合蛋白-D28k和小白蛋白，而在疾病后期受损或很少受损的运动神经元（即Onuf核运动神经元、动眼神经、滑车神经和展神经神经元）表达明显更高水平的免疫反应性钙结合蛋白-D28K和/或小白蛋白。运动神经元-神经母细胞瘤VSC 4.1杂交细胞在二丁酰环磷酸腺苷诱导分化后丧失免疫反应性钙结合蛋白-D28k和小白蛋白，并被ALS患者的IgG杀死。未分化的钙结合蛋白/小白蛋白反应性VSC 4.1细胞未被杀死，表达高水平钙结合蛋白-D28K和小白蛋白免疫反应性的其他细胞系（黑质-神经母细胞瘤杂交细胞和N18TG2神经母细胞瘤亲代细胞）也未被杀死。这些研究表明，钙结合蛋白-D28K和小白蛋白免疫反应性降低可能有助于解释ALS中运动神经元的选择性易损性。
