Nihei K, McKee A C, Kowall N W
Neurology Service, Massachusetts General Hospital, Boston 02114.
Acta Neuropathol. 1993;86(1):55-64. doi: 10.1007/BF00454899.
We examined patterns of neuronal degeneration in the motor cortex of amyotrophic lateral sclerosis (ALS) patients using traditional cell stains and several histochemical markers including neurofilament, parvalbumin, NADPH-diaphorase, ubiquitin, Alz-50 and tau. Three grades of ALS (mild, moderate, severe) were defined based on the extent of Betz cell depletion. Non-phosphorylated neurofilament immunoreactive cortical pyramidal neurons and non-pyramidal parvalbumin local circuit neurons were significantly depleted in all grades of ALS. In contrast, NADPH-diaphorase neurons and Alz-50-positive neurons were quantitatively preserved despite reduced NADPH-diaphorase cellular staining and dendritic pruning. The density of ubiquitin-positive structures in the middle and deep layers of the motor cortex was increased in all cases. Axonal tau immunoreactivity was not altered. These histochemical results suggest that cortical degeneration in ALS is distinctive from other neurodegenerative diseases affecting cerebral cortex. Unlike Huntington's disease, both pyramidal and local cortical neurons are affected in ALS; unlike Alzheimer's disease, alteration of the neuronal cytoskeleton is not prominent. The unique pattern of neuronal degeneration found in ALS motor cortex is consistent with non-N-methyl-D-aspartate glutamate receptor-mediated cytotoxicity.
我们使用传统细胞染色法以及包括神经丝、小白蛋白、还原型辅酶Ⅱ黄递酶、泛素、Alz-50和tau在内的几种组织化学标志物，研究了肌萎缩侧索硬化症（ALS）患者运动皮层中的神经元变性模式。根据贝茨细胞缺失程度定义了三个等级的ALS（轻度、中度、重度）。在所有等级的ALS中，非磷酸化神经丝免疫反应性皮层锥体神经元和非锥体小白蛋白局部回路神经元均显著减少。相比之下，尽管还原型辅酶Ⅱ黄递酶细胞染色减少和树突修剪，但还原型辅酶Ⅱ黄递酶神经元和Alz-50阳性神经元在数量上得以保留。在所有病例中，运动皮层中层和深层泛素阳性结构的密度均增加。轴突tau免疫反应性未改变。这些组织化学结果表明，ALS中的皮层变性与影响大脑皮层的其他神经退行性疾病不同。与亨廷顿舞蹈症不同，ALS中锥体神经元和局部皮层神经元均受影响；与阿尔茨海默病不同，神经元细胞骨架的改变并不突出。在ALS运动皮层中发现的独特神经元变性模式与非N-甲基-D-天冬氨酸谷氨酸受体介导的细胞毒性一致。
