EFECTS OF DEMYELINATION AND AGING UPON SODIUM CHANNELS

脱髓鞘和衰老对钠通道的影响

• 批准号: 3768397
• 负责人: JOHN D ENGLAND
• 金额: --
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3768397
• 关键词: Alzheimer's disease; aging; alternatives to animals in research; animal old age; antibody; axon; brain disorder diagnosis; doxorubicin; goldfish; human tissue; immunocytochemistry; laboratory rat; myelinopathy; neural conduction; peripheral nervous system; postmortem; sodium channel; tellurium; tunicamycin

The sodium channel is a transmembrane protein that mediates the voltage dependent sodium permeability of electrically excitable membranes. Its presence is of obvious importance for the generation and propagation of action potentials along axolemma. Using well characterized antibodies directed against sodium channels and immunocytochemical/radioimmunoassay methods, we plan to study separately how experimental demyelination and aging affect sodium channels in nervous tissues. In the first set of observations we will determine and contrast sodium channel distribution and quantity along peripheral nerve axons demyelinated acutely with potassium tellurite, subacutely with tunicamycin, and chronically with doxorubicin. These studies should help us understand how demyelinated axons become remodelled to re-establish conduction. Such information is important since the resumption of axonal conduction appears to be the basis for recovery in many human demyelinating diseases. In the second set of observations we will determine sodium channel distribution and quantity in aged nervous tissue and contrast this with their distribution and quantity in young nervous tissue. An established and well studied aging rat colony will provide ample aged brain and peripheral nerve for one part of this study. In a separate series of observations we will examine sodium channels in human brain tissue affected by diseases associated with aging. A special interest will be the examination of postmortem brain afflicted with Alzheimer's disease. These studies should reveal whether aging per se or diseases associated with aging result in biochemically detectable changes in sodium channels that could culminate in neuronal dysfunction. Such information is important since little is known regarding the mechanisms by which aging or diseased neurons lose their ability to function.

钠通道是一种跨膜蛋白，介导电压 依赖于电可兴奋膜的钠渗透性。 其 存在对于产生和传播是明显重要的 沿着轴膜的动作电位。 使用充分表征的抗体 针对钠通道和免疫细胞化学/放射免疫测定 方法，我们计划分别研究实验性脱髓鞘和 衰老影响神经组织中的钠通道。 在第一组观察中，我们将确定和对比钠 沿着周围神经轴突脱髓鞘的通道分布和数量 亚碲酸钾急性，衣霉素亚急性， 长期服用阿霉素 这些研究应该能帮助我们理解 脱髓鞘的轴突被重塑以重新建立传导。 等 信息是重要的，因为轴突传导的恢复出现 是许多人类脱髓鞘疾病康复的基础。 在第二组观察中，我们将确定钠通道 在老年神经组织中的分布和数量，并与 它们在年轻神经组织中的分布和数量。 一个既定 经过充分研究的老龄大鼠群体将提供充足的老年大脑， 外周神经是这项研究的一部分。 在一个单独的系列， 我们将研究受影响的人脑组织中的钠通道 与衰老有关的疾病。 一个特别的兴趣将是 对患有阿尔茨海默病的死后大脑的检查。 这些 研究应该揭示衰老本身或与之相关的疾病 衰老导致钠通道发生生化可检测的变化， 会导致神经元功能紊乱 这些信息很重要 由于对衰老或疾病的机制知之甚少， 神经元失去了功能。