THE AGING BRAIN: IMMUNOHISTOLOGY AND BIOCHEMISTRY

这个项目的目的是为了了解生物和分子 神经系统衰老的发病机制。阿尔齐希默氏病是 最常见的器质性痴呆症见于老年。在这种疾病中，一种重要的 组织病理学损害是指存在神经原纤维缠结， 主要含有成对的螺旋状细丝。 针对几种正常神经纤维蛋白的抗体已经被 用来研究缠结的分子性质。可用的信息 表明缠结与神经丝具有共同的抗原决定簇。 蛋白质和波形蛋白。目前尚不清楚是否涉及其他元素 纠缠在一起。最近用部分纯化的小鼠免疫小鼠 免疫小鼠脾的缠结组份及其后续杂交 细胞与骨髓瘤细胞，我们制备了抗缠结的单抗。 该抗体不识别轴突中的神经细丝或HeLa中的波形蛋白 但与HeLa细胞核和有丝分裂纺锤体结合。的身份 这种缠结相关抗原及其在细胞中的作用 部门将是我们继续学习的主题之一。在……里面 此外，我们建议用部分纯化的疫苗免疫更多的小鼠。 神经原纤维缠结，并产生一组针对 缠结的不同决定因素。这些抗体将被用来 确定缠结是否包含病理特定成分或其他 正常的大脑成分，以提供进一步的证据表明纠缠和 神经丝蛋白和波形蛋白具有共同的免疫学特性 并进一步净化纠缠。 之前资助的另一个项目涉及大脑的分布 周围神经系统(PNS)中的胶质细丝蛋白(GFP)。我们 已经证明，在PNS中，GFP主要分布在Schwann 与无髓轴突相关的细胞及中枢神经系统和三叉神经节的绿色荧光蛋白 具有共同的生化特性。在持续进修方面，我们建议 确定轴突是否支配雪旺细胞中绿色荧光蛋白的表达。我们会 使用超微结构、免疫组织化学和生化技术 检查分离的神经残端，交叉吻合的有髓神经和 成年大鼠的无髓神经。

This project is aimed at understanding the biology and molecular pathogenesis of aging in the nervous system. Alzehimer's disease is the most common organic dementia seen in old age. In this disease an important histopathological lesion is the presence of neurofibrillary tangles which contain mostly paired helical filaments. Antibodies raised against several normal neurofibrous proteins have been used to study the molecular nature of tangles. Information available indicates that tangles share antigenic determinants with neurofilament protein and vimentin. It is unknown if additional elements are involved in making tangles. Recently by immunization of mice with a partially purified tangle fraction and subsequent hybridization of an immunized mouse spleen cells with myeloma cells, we produced a monoclonal anti-tangle antibody. This antibody does not recognize neurofilament in axons or vimentin in HeLa cells but bind to HeLa cell nuclei and mitotic spindle. The identity of this tangle-related antigen and the function of the antigen in cell division will be one of the subjects of our continuing studies. In addition, we proposed to immunize more mice with partially purified neurofibrillary tangles and raise a panel of monoclonal antibodies against different determinants of the tangles. These antibodies will be used to determine if tangles contain pathologic specific components or additional normal brain components, to provide further evidence that tangles and neurofilament proteins and vimentin have common immunological properties and to further purify tangles. A separate project funded previously concerns the distribution of brain glial filament protein (GFP) in the peripheral nervous system (PNS). We have demonstrated that in PNS the GFP is distributed primarily in Schwann cells associated with unmyelinated axons and that the GFP of CNS and PNS have common biochemical properties. In continuing studies, we propose to determine if axons dictate the expression of GFP in Schwann cells. We will use ultrastructural, immunohistochemical and biochemical techniques to examine isolated nerve stumps, cross-anastomosed myelinated and unmyelinated nerves of adult rats.