Neuropathological study of neuronal abnormalities showing αB crystallin expression

显示 αB 晶状体蛋白表达的神经元异常的神经病理学研究

• 批准号: 10670607
• 负责人: MIZUTANI Tomohiko
• 金额: $ 1.73万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670607/
• 关键词: αB crystallin; ballooned neuron; Lewy body; Neuronal abnormality; ユビキチン陽性封入体; 上衣細胞

αB-crystallin (αB-C) is a subunit of α-crystallin, a major protein component of the vertebrate lens, and αB-C expression has been reported in extra-lenticular tissues. In normal brains, oligodendrocytes and astrocytes are stained with anti-αB-C antibody, but neurons are not. Since most of previous studies using this antibody have primarily dealt with ballooned neurons, we investigated such αB-C expression in neuronal abnormalities of various neurological diseases.We examined 73 patients with 29 kinds of neurological diseases and 4 patients with non-neurological diseases. We obtained 4-μm paraffin embadded sections of the spinal cords from all of the patients, in addition to the sections of some areas of the brains involved by neurological diseases. Each section was stained by the routine staining methods and avidin-biotin complex (ABC) method (Vectastain elite, Vector) using anti-αB-C antibody (a gift from Dr. Hiroshi Mori). The anti-αB-C antibody was made by the injection of a synthet … More ic peptide from the carboxyl terminal of αB-C to rabbits (Tamaoka et al, 1995).Frequent immunoreactivity to αB-C included ballooned neurons in corticobasal degeneration (CBD) and Pick's disease, cortical Lewy bodies, ballooned in a new type of familial Parkinson disease (Mizutani et al, 1998), and renurons of the inferior olives with pseudohypertrophy in 2 out of 3 cases. Occasional immunoreactivity was observed in some neurons around cerebral infarcts. Rare immunoreactivity included the anterior hom motor neurons of the spinal cords in amyotrophic lateral sclerosis (ALS), progressive supranuclear palsy (PSP), Machado-Joseph disease, inclusion body myositis, multiple sclerosis, and carcinomatous meningitis, as well as the posterio hom neurons of the spinal cords in ALS, PSP, hepatic myelopathy, inclusion body myositis, and crytococcal meningitis. In the spinal cords, no consistent relationship was observed between the αB-C immunostaining and the kind of diseases, and between the αB-C immunostaining and the distribution of the histopathological lesions. Rare immunoreactivity was also found in the pontine nuclei neurons of multiple system atrophy and CBD. Negative immunoreactivity to αB-C included Pick bodies, brainstem Lewy bodies, Alzheimer's neurofibrillary tangles, and neurons with central chromatolysis.Our results indicated that αB-C immunostaining to abnormal neurons was selective, and that this staining was useful to detect ballooned neurons and cortical Lewy bodies, and to differentiate balloned neurons from both Pick bodies and neurons with central chromatolysis due to axonal injury. Although neuronal immunoreactivity was observed in other various histopathological lesions, this abnormality was rare, and further studies are needed to clarify the significance of such neuronal immunoreactivity. Less

αB-晶体蛋白(αB-C)是脊椎动物晶状体的主要蛋白质成分α-晶体蛋白的一个亚基，αB-C在晶状体外组织中有表达。在正常大脑中，少突胶质细胞和星形胶质细胞被抗αB-C抗体染色，但神经元没有。由于以往使用该抗体的研究主要针对气球状神经元，因此我们研究了αB-C在各种神经系统疾病的神经元异常中的表达。我们获得了所有患者脊髓的4-μm石蜡包埋切片，以及神经疾病涉及的大脑部分区域的切片。每个切片用常规染色方法和亲和素-生物素复合体(Vectaain Elite，Vectaain Elite)法染色，抗αB-C抗体(森博智博士赠送的礼物)。抗αB-C抗体是通过注射合成的…制备的对αB-C的免疫反应常见的包括皮质基底性变性和皮克氏病中的神经元气球，一种新型家族性帕金森病中的皮质路易体(Mizutani等人，1998年)，以及2/3的下橄榄肾单位伴有假性肥大。脑梗塞周围部分神经元偶见免疫反应。少见的免疫反应包括肌萎缩侧索硬化症(ALS)、进行性核上性麻痹(PSP)、马查多-约瑟夫病、包涵体肌炎、多发性硬化症和癌性脑膜炎的脊髓前角运动神经元，以及ALS、PSP、肝性脊髓病、包涵体肌炎和隐球菌性脑膜炎的脊髓后角运动神经元。在脊髓中，αB-C免疫染色与疾病类型、αB-C免疫染色与组织学病变的分布之间没有一致的关系。在多系统萎缩和CBD的脑桥核神经元中也发现了罕见的免疫反应。αB-C免疫反应阴性的神经元包括Pick小体、脑干路易小体、阿尔茨海默病神经原纤维缠结和中枢性色素溶解神经元。结果表明，αB-C免疫染色对异常神经元具有选择性，这种染色有助于检测气球状神经元和皮质路易小体，并有助于区分Pick小体和中枢性色解神经元。虽然在其他不同的组织病理损伤中也观察到神经元免疫反应，但这种异常是罕见的，需要进一步的研究来阐明这种神经元免疫反应的意义。较少

项目成果

Mizutani T,et al.: "Atypical neurofibrillary tangees stained with α-synuclein/NACP"Journal of Neuropathology and Experimental Neurology. 58(5). 554 (1999)

Mizutani T 等人：“用 α-突触核蛋白/NACP 染色的非典型神经原纤维”，《神经病理学和实验神经学杂志》58(5) (1999)。

Sasaki S. et al.: "Familial amyotrophic lateral sclerosis with widespread vamolation and hyaline inclusions."Neurology. 51. 871-875 (1998)

Sasaki S. 等人：“家族性肌萎缩侧索硬化症，伴有广泛的静脉曲张和透明包涵体。”神经病学。

Sasaki S, Ohsawa Y, Yamane K, Sakuma H, Shibata N, Nakano R, Kikukawa K, Mizutani T, Tsuji S, Iwata M: "Familial amyotrophic lateral sclerosis with widespread vacuolation and hyaline inclusions."Neurology. 51. 871-875 (1998)

Sasaki S、Ohsawa Y、Yamane K、Sakuma H、Shibata N、Nakano R、Kikukawa K、Mizutani T、Tsuji S、Iwata M：“具有广泛空泡和透明包涵体的家族性肌萎缩侧索硬化症。”神经病学。

Mizutani T, et al.: "Novel, vbiquitin-positive inclusievs in the epevdymal cells of the spinal lord and caudal medulla."Journal of Neuropathology and Experimental Neurology. 57. 507 (1998)

Mizutani T 等人：“脊髓主和尾髓质的附膜细胞中存在新颖的、vbiquitin 阳性的包含物。”《神经病理学和实验神经病学杂志》。

Mizutani T, Arima K, Ueda K, Ozawa T, Mochizuki Y, Kakimi S, Hirai S, Tsuji S, and Takasu T: "Atypical neurofibrillary tangles stained with α-synuclein/NACP."Journal of Neuropathology and Experimental neurology. 58. 554 (1998)

Mizutani T、Arima K、Ueda K、Ozawa T、Mochizuki Y、Kakimi S、Hirai S、Tsuji S 和 Takasu T：“用 α-突触核蛋白/NACP 染色的非典型神经原纤维缠结”58。 554 (1998)