PSYCHOPATHOLOGY OF THE AGING: CELL MEMBRANE CORRELATES

衰老的心理病理学：细胞膜相关

• 批准号: 3068684
• 负责人: GEORGE S ZUBENKO
• 金额: $ 6.61万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3068684
• 关键词: aging; biophysics; cell age; cell membrane; cell population study; dementia; erythrocyte membrane; fluorescence spectrometry; histopathology; human subject; membrane activity; membrane lipids; platelet aggregation; platelets; postmortem; synaptosomes

This research proposal employs fluorescence spectroscopy as a tool to probe the biophysical characteristics of blood cell and brain synaptosomal membranes from patients with Alzheimer's disease. (1) Studies of platelet and RBC membranes may reveal characteristic alterations that may aid in the antemortem diagnosis of Alzheimer's disease. The relationship of observed alterations in blood cell membranes from patients with alzheimer's disease to the demographic and clinical (age at onset, duration, severity, sleep EEG indices) characteristics of this group will be investigated. (2) experiments will also be conducted to determine whether alterations in blood cell membranes from Alzheimer patients reflect a generalized platelet or RBC membrane "defect" or a change in the age-distribution of these cells. In addition to this important clarification, these experiments will provide information on cell membrane changes that accompany the normal aging process of peripheral blood cells. (3) The functional consequence of biophysical abnormalities of platelet membranes will be determined using platelet aggregation as a model system. (4) A parallel study of synaptosomal membranes prepared from fresh, unfixed regions of Alzheimer brain will provide information on membrane biophysical properties as correlated with histopathologic reports. It will, therefore, be possible to determine whether any identified alterations in these synaptosomal membrane properties are more widespread than the characteristic histopathologic abnormalities of Alzheimer's disease and whether the membrane changes are likely to antedate neuronal degeneration and cell loss. To accomplish the proposed research plan, the candidate will obtain additional supervised experience in: (1) blood cell and synaptosomal membrane isolation; (2) the theory and techniques of fluorescence spectroscopy; and (3) the design, execution, and analysis of clinical research studies.

这项研究建议采用荧光光谱作为一种工具， 血细胞和脑突触体的生物物理特性 阿尔茨海默病患者的细胞膜。 (1)血小板研究 红细胞膜可能揭示特征性的改变，这可能有助于 阿尔茨海默病的死前诊断 观察到的关系 阿尔茨海默病患者血细胞膜的改变 人口统计学和临床（发病年龄、持续时间、严重程度、睡眠 EEG指标）的特点，这组将进行调查。 （二） 还将进行实验，以确定是否改变 阿尔茨海默氏症患者的血细胞膜反映了广泛的血小板 或红细胞膜“缺陷”或这些细胞的年龄分布的变化， 细胞 除了这一重要的澄清，这些实验将 提供伴随正常细胞膜变化的信息， 外周血细胞的老化过程。 (3)的功能后果 血小板膜的生物物理异常将使用 血小板聚集作为模型系统。 (4)平行研究 从阿尔茨海默病的新鲜、未固定区域制备的突触体膜 大脑将提供关于膜生物物理特性的信息， 与组织病理学报告相关。 因此， 以确定这些突触体中是否有任何已识别的改变， 膜的特性比特性更广泛 阿尔茨海默病的组织病理学异常以及 膜变化可能先于神经元变性和细胞损失。 为了完成拟议的研究计划，候选人将获得 额外的监督经验：（1）血细胞和突触体 膜分离技术;（2）荧光理论与技术 光谱学;和（3）临床的设计，执行和分析 调查研究。