AUTOIMMUNITY TO NEURAL ACETYLCHOLINESTERASE

借助于脑乙酰胆碱酯酶的单克隆抗体 乙酰胆碱酯酶（AChE），一种新的胆碱能功能障碍的自身免疫模型， 在老鼠身上创造的。 一种抗体有惊人的聚集趋势 中枢神经系统（CNS）中的神经元有可能导致 广泛的异常 建议研究以下因素： 促进这种抗体到达大脑中的靶点， 表征其介导的结构和化学异常 那里 这项工作可能会完善我们的概念，血脑屏障， 与免疫球蛋白的关系 该实验系统还具有 提供神经退行性疾病相关数据的潜力 中枢胆碱能系统，包括阿尔茨海默病。 另一组 的实验将利用无法获得乙酰胆碱酯酶的抗体 中枢神经系统中的抗原表位。 当全身注射时，这些抗体 诱发一种新节前交感神经紊乱，但 对其他胆碱能系统的明显影响极小。 计划在 研究节前神经节的破坏机制 交感神经终端和地图的细胞分布， 免疫损伤 乙酰胆碱酯酶抗体对 运动和副交感神经系统也将在 详细 将特别注意防止出现这种情况的因素。 抗体中交感神经末梢的正常再生反应 治疗大鼠并导致永久性自主神经功能障碍。 最后，尝试 将决定哪种类型的人类 自主神经功能障碍可能具有类似的自身免疫机制。

With the aid of monoclonal antibodies to brain acetylcholinesterase (AChE), a new autoimmune model of cholinergic dysfunction has been created in rats. One antibody with a surprising tendency to accumulate in the central nervous system (CNS) has the potential to cause widespread abnormalities. It is proposed to study the factors that facilitate the access of this antibody to targets in the brain and to characterize the structural and chemical abnormalities that it mediates there. This work may refine our concepts of the blood brain barrier in relation to immunoglobulins. The experimental system also has the potential to provide data relevant to neurodegenerative diseases of central cholinergic systems, including Alzheimer's disease. Another set of experiments will utilize antibodies that do not have access to ACHE epitopes in the CNS. When injected systemically, these antibodies induce a novel disorder of preganglionic sympathetic nerves but have minimal apparent effects on other cholinergic systems. It is planned to investigate the mechanisms of destruction of the preganglionic sympathetic terminals and to map out the cellular distribution of the immunologic damage. The more modest effects of AChE-antibodies on the motor and parasympathetic nervous systems will also be examined in detail. Special attention will be focused on the factors that prevent a normal regenerative response of sympathetic terminals in antibody treated rats and result in permanent dysautonomia. Finally, attempts will be made to determine which of the several types of human dysautonomias might have a similar autoimmune mechanism.