Shibata N, Asayama K, Hirano A, Kobayashi M
Department of Pathology, Tokyo Women's Medical College, Japan.
Dev Neurosci. 1996;18(5-6):492-8. doi: 10.1159/000111445.
A role mutations in the superoxide dismutase (SOD)-1 gene in the pathogenesis of amyotrophic lateral sclerosis (ALS) has been discussed. To investigate immunohistochemical alterations of SOD in the spinal cord affected with the disease, we examined 3 patients with SOD1 mutation-associated family with ALS, 20 patients with sporadic ALS and 10 control individuals. Lewy body-like hyaline inclusions (LBHIs) were seen in the anterior horn cells of all the familial patients and 10 of the 20 sporadic patients, while skein-like inclusions (SIs) and Bunina bodies (BBs) were present in the 20 sporadic patients but not in the familial patients. The primary antibodies used for immunostaining were rabbit antisera raised against human SOD1 and SOD2. The anti-SOD1 antibody reacted strongly with all LBHIs of each familial patient and with some LBHIs of each sporadic patient. The cytoplasm of morphologically intact and degenerated spinal cord neurons as well as spheroids seen in the cases examined was only weakly stained by the antibody to SOD1 or not at all. The reactive astrocytes displayed weak to moderate staining for SOD1. The anti-SOD2 antibody strongly immunolabeled the reactive astrocytes and microglia. LBHIs of both familial and sporadic ALS were negatively stained for SOD2. Spinal cord neurons and spheroids of each case exhibited no significant SOD2 immunoreactivity. Neither antibodies reacted with SIs nor BBs. These results indicate that SOD1 may be involved in the formative process of LBHIs especially in familial ALS but not always in that of SIs or BBs, and imply that SOD2 may have no connection with any of these ALS-related abnormal structures.
超氧化物歧化酶（SOD）-1基因的突变在肌萎缩侧索硬化症（ALS）发病机制中的作用已被探讨。为研究疾病累及脊髓中SOD的免疫组化改变，我们检查了3例SOD1突变相关家族性ALS患者、20例散发性ALS患者和10名对照个体。在所有家族性患者以及20例散发性患者中的10例的前角细胞中可见路易小体样透明包涵体（LBHIs），而20例散发性患者中有丝状包涵体（SIs）和布尼亚小体（BBs），但家族性患者中没有。用于免疫染色的一抗是针对人SOD1和SOD2产生的兔抗血清。抗SOD1抗体与每个家族性患者的所有LBHIs以及每个散发性患者的一些LBHIs强烈反应。在所检查病例中，形态完整和变性的脊髓神经元的细胞质以及球状体仅被抗SOD1抗体弱阳性染色或根本未被染色。反应性星形胶质细胞对SOD1呈弱阳性至中度染色。抗SOD2抗体强烈免疫标记反应性星形胶质细胞和小胶质细胞。家族性和散发性ALS的LBHIs对SOD2呈阴性染色。每个病例的脊髓神经元和球状体均未显示出明显的SOD2免疫反应性。两种抗体均未与SIs或BBs反应。这些结果表明，SOD1可能参与LBHIs的形成过程，尤其是在家族性ALS中，但并非总是参与SIs或BBs的形成过程，这意味着SOD2可能与这些ALS相关的异常结构均无关联。
