Relationship between motor neuron disease with basophilic inclusions and frontotemporal dementia

嗜碱性包涵体运动神经元病与额颞叶痴呆的关系

基本信息

批准号：
12670628
负责人：
KUSAKA Hirofumi
金额：
$ 1.86万
依托单位：
Kansai 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：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670628/
关键词：
motor neuron disease basophilic inclusion Golgi apparatus ALS frontotemporal dementia immunohistochemistry cystatin C 封入体単離

motor neuron disease basophilic inclusion Golgi apparatus ALS frontotemporal dementia immunohistochemistry cystatin C 封入体単離

项目摘要

To clarify the significance of inclusion formation for neurodegeneration in patients with adult-onset atypical motor neuron disease with basophilic inclusions, in the present study we have attempted to analyze constituents of the inclusion. For this purpose, we investigated immunohistochemically the formalin-fixed, paraffin-embedded brain and spinal cord sections obtained from autopsy, using various primary antibodies as follows ; anti-ubiquitin, anti-Abeta, anti-phosphorylated neurofilament, anti-MAP subtypes, anti-actin, anti-vimentin, anti-SOD1, anti-alfa-synuclein, and anti-cystatin C. Unfortunately, most of these primary antibodies had not immunoreacted with the inclusions, except antibodies to ubiquitin and cystatin C, with which the inclusions showed deposits of a granular reaction products. Since cystatin C is a Golgi apparatus-related protein, we had applied antibodies againsto other repaltd proteins, MG160 and trans-Golgi-network, for further investigation. However, these ant … More ibodies had not immunostained the inclusions. On the other hand, the anti-MG160 antibody clearly recognized Golgi apparaatus of normal-looking anterior horn cells in the form of larger, angular, or elongated profiles. In contrast, all neurons bearing the basophilic inclusions showed fragmentation and reduced number of the Golgi apparaatus. These findings were similar to the previously reported observaations in motor neurons of classic ALS patients and of mutant SOD1 transgenic mice.Therefore, our findings suggest that the formation of the basophilic inclusions may not represent a protective reaction for the isolation of harmful products, but may contribute to irreversible neurodegeneration. Furthermore, our results indicate that common pathogenetic mechanisms may be involved in the formation of the basophilic inclusions and in the fragmentation of the Golgi apparatus. In addition, the present observations imply that the adult-onset atypical motor neuron disease with basophilic inclusions, classic ALS and mutant SOD1 transgenic mice may share similar neurodegeneration process, the fragmentation of the Golgi apparatus being as an earlier sign. Less

为了阐明包容性形成对具有嗜碱性包含的成人发作非典型运动神经元疾病患者的神经变性的重要性，在本研究中，我们试图分析包容性的构成。为此，我们使用各种主要的原代抗体，从尸检中研究了福尔马林固定的，石蜡包裹的脑和脊髓切片的免疫组织化学；抗泛素，抗abeta，抗磷酸化的神经丝，抗图亚型，抗肌动蛋白，抗肌动蛋白，抗毒素，抗SOD1，抗SOD1，抗阿尔法核蛋白和抗cystatin和抗cystatin C.不幸的是，这些主要抗体除了对抗体的包含，除了抗生素外，大多数是对抗生素除外的，夹杂物显示出颗粒反应产物的沉积物。由于胱抑素C是一种与高尔基体相关的蛋白质，因此我们采用了针对其他重型蛋白MG160和Trans-Golgi-NetWork的抗体，以进行进一步研究。但是，这些蚂蚁……更多的ibodies并未免疫夹杂物。另一方面，抗MG160抗体以较大，角或伸长的特征的形式清楚地识别出正常前角细胞的高尔基体。相比之下，所有带有嗜碱性夹杂物的神经元均表明碎裂和高尔基体数量减少。这些发现与先前报道的经典ALS患者的运动神经元和突变SOD1转基因小鼠的观察结果相似。因此，我们的发现表明，嗜碱性夹杂物的形成可能不能代表隔离有害产物的保护反应，但可能有助于不可逆的神经脱发。此外，我们的结果表明，常见的致病机制可能与嗜碱性包容物的形成和高尔基体的碎片化有关。此外，目前的观察结果表明，具有嗜碱性包含，经典ALS和突变的SOD1转基因小鼠的成年非典型运动神经元疾病可能具有相似的神经变性过程，Golgi Appatus的碎片是早期的征兆。较少的