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

ALS 中的 EAAT1 和 EAAT2 免疫反应性以及 SOD1 (G93A) 转基因小鼠的病理学

基本信息

批准号：
11670646
负责人：
SASAKI Shoichi
金额：
$ 1.98万
依托单位：
Tokyo Women's Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670646/
关键词：
ALS EAAT1 EAAT2 SOD1 mutation transgenic mice iNOS nitrotyrosine spinal cord 筋萎縮性側素硬化症トランスジュニックマウス SCDI変異 nitric oxide synthase 免疫組織学グルタミン酸トランスポーター免疫組織

项目摘要

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

我们用免疫化学方法研究了肌萎缩侧索硬化症（ALS）患者的脊髓，使用EAAT 1和EAAT 2抗体来检查EAAT 1和EAAT 2免疫反应性与前角神经元变性之间的关系。在对照组中，脊髓灰质被抗体密集免疫染色，而白色物质通常不被免疫染色。在ALS患者中，EAAT 1免疫反应性在灰质中保存相对良好。与此相反，EAAT 2免疫反应性与前角细胞的神经元损失的程度：在轻度神经元耗竭的患者，前角密集的抗体免疫染色，而在严重的神经元损失的患者，EAAT 2的表达显着减少。因此，我们证明了EAAT 1和EAAT 2免疫反应性在ALS进展的不同阶段的差异，作为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检查， ...更多信息研究了具有G93 A突变SOD 1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性的时间和地形分布，从而阐明了在神经变性过程中运动系统的氧化损伤增加的可能作用。对照组小鼠在各年龄段均未见iNOS或NT免疫反应阳性。相反，在转基因小鼠中，在24周时，（早期症状前期），前角神经元偶见iNOS和NT免疫染色;（晚期症状前期），免疫组化染色并不少见;在32周（早期症状阶段）和35周（终末期），iNOS和NT免疫反应阳性细胞主要见于增殖反应性星形胶质细胞和前角细胞胞体。iNOS和NT免疫阳性反应选择性地定位于前角神经元，提示氧化应激可能参与了该转基因小鼠运动神经元变性的病理机制。少