EAAT1 and EAAT2 immunoreactivity in ALS and pathology of SOD1 (G93A) transgenic mice

我们对肌萎缩侧索硬化症(ALS)患者的脊髓进行了免疫组织化学研究，用EAAT1和EAAT2抗体来检测EAAT1和EAAT2免疫反应与前角神经元变性的关系。在对照组，脊髓灰质被抗体进行了密集的免疫染色，而白质一般不被免疫染色。在ALS患者中，EAAT1免疫反应在灰质中相对保存良好。相反，EAAT2在前角的免疫阳性反应与前角细胞的神经元丢失程度相关：在轻度神经元缺失的患者中，EAAT2的表达被抗体密集染色，而在严重的神经元丢失的患者中，EAAT2的表达明显减少。因此，我们证明在ALS的不同进展阶段，EAAT1和EAAT2的免疫反应性是不同的，这是这种疾病的病理机制的一个特征。我们还进行了免疫组织化学S…进一步研究了带有G93A突变SOD1基因的转基因小鼠的脊髓，使用诱导型一氧化氮合酶(INOS)和硝基酪氨酸(NT)的抗体来表征免疫反应的时间和地形分布，从而阐明了运动系统氧化损伤增加在神经退化过程中的可能作用。对照组小鼠各年龄段均未见iNOS或NT免疫反应阳性。而在转基因小鼠中，24周(症状前期)时，前角神经元偶见iNOS和NT免疫反应阳性，28周时(症状前期)，iNOS和NT免疫反应阳性，32周(症状早期)和35周(终末期)时，iNOS和NT免疫阳性反应常见于增殖反应阳性的星形胶质细胞和前角细胞的胞体中。INOS和NT免疫反应在前角神经元的选择性定位表明，氧化应激可能参与了转基因小鼠运动神经元变性的病理机制。较少

We immunohistochemically investigated the spinal cord of patients with amyotrophic lateral sclerosis (ALS), using EAAT1 and EAAT2 antibodies to examine relationships between EAAT1 and EAAT2 immunoreactivity and degeneration of anterior horn neurons. In controls, spinal cord gray matter was densely immunostained by antibodies, whereas the white matter was generally not immunostained. In ALS patients, EAAT1 immunoreactivity was relatively well-preserved in the gray mater. In contrast, EAAT2 immunoreactivity in anterior horns correlated with the degree of neuronal loss of anterior horn cells : in the patients with mild neuronal depletion, anterior horns were densely immunostained by the antibody, whereas in the patients with severe neuronal loss, EAAT2 expression was markedly reduced. Thus, we demonstrate a difference in EAAT1 and EAAT2 immunoreactivity in different stages of progression in ALS, as a feature of the pathomechanism of this disease. We also performed an immunohistochemical s … More tudy of the spinal cords of transgenic mice with a G93A mutant SOD1 gene, using antibodies to inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT) to characterize the temporal and topographic distribution of the immunoreactivity, thus illuminating the possible role of increased oxidative damage to the motor system in the neurodegenerative process. The control mice showed no positive iNOS or NT immunoreactivity at any age. In contrast, in the transgenic mice, at 24 weeks (early presymptomatic stage), the anterior horn neurons were occasionally immunostained for iNOS and NT ; at 28 weeks (late presymptomatic stage), they were not uncommonly immunostained ; at 32 weeks (early symptomatic stage) and 35 weeks (end-stage), positive iNOS and NT immunoreactivity was frequently observed in proliferated reactive astrocytes as well as in the somata of the anterior horn cells. The selective localization of positive iNOS and NT immunoreactivity in the anterior horn neurons suggests that oxidative stress may be involved in the pathomechanism of degeneration of motor neurons in this transgenic mice. Less