AMYGDALA IN ALZHEIMER'S DISEASE AND NORMAL AGING

杏仁核在阿尔茨海默病和正常衰老中的作用

• 批准号: 3119973
• 负责人: JOSEPH B ROGERS
• 金额: $ 15.44万
• 依托单位: BANNER SUN HEALTH RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-15 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3119973
• 关键词: Alzheimer's disease; Parkinson's disease; aging; amygdala; cellular pathology; electron microscopy; epilepsy; hippocampus; human tissue; interneurons; morphology; neuritic plaques; neuroanatomy; neurofibrillary tangles; somatostatin

The overall goal of this research proposal is to elucidate morphologic relations and alterations of neurons in human amygdala obtained at autopsy from normal aged individuals and those afflicted with Alzheimer's disease (AD). The amygdala occupies a strategic position in the circuitry of the limbic system, maintaining connections between cortical association areas and visceral-associated nuclei located subcortically, and undergoes severe pathologic alterations in AD. The first aim is to determine whether pathological alterations resulting from AD have predilection for specific amygdaloid nuclei. Initial morphometric analyses seek to determine whether amygdaloid atrophy in AD correlates with decreased neuronal-packing density, reduced neuronal size or neuron loss. The topographic distribution of neuritic plaques (NPs) and neurofibrillary tangles (NFTs) will be mapped using thioflavin S to test the hypothesis that certain amygdaloid nuclei are selectively vulnerable in AD. Amygdaloid nuclei with severe, intermediate and negligible levels of pathology will be selectively studied at the ultrastructural level to ascertain synaptic relations between normal and pathologically altered structures, and to determine whether alterations in synaptic length and synaptic density correlate with AD. The second aim is to determine the relationship between NFTs in cortical and amygdaloid projection neurons, and NPs in several of their respective terminal fields. Data from morphometric analyses of temporal cortical areas, including hippocampal formation and subcortical nuclei connectionally related to the amygdala will be used to test for a transneuronal effect in the pathogenesis of AD. The third aim entails using experimental neuroanatomical techniques to determine the relationships between intrinsic neurons and AD pathology in chemically defined populations of amygdaloid neurons. The structural substrate of intrinsic neurons and their synaptic relations will be analyzed with light and electron microscopy using NADPH histochemistry and antisera against somatostatin (SOM) and neuropeptide tyrosine (NPY). The results of this research are relevant to a wide range of basic and clinical neuroscience research. The amygdala figures prominently in limbic circuitry and interruptions of this circuitry cause debilitating deficits in memory, attention and affect. Results of these studies will provide qualitative and quantitative information fundamental to understanding structure-function relationships at the synaptic level in normal aged individuals, as well as in neurological disorders such as epilepsy, Alzheimer's and Parkinson's diseases.

这项研究提案的总体目标是阐明形态 人杏仁核神经元的相互关系和变化 正常老年人和阿尔茨海默病患者的尸检 疾病(AD)。杏仁核在大脑中占有重要地位。 边缘系统的回路，维持大脑皮层之间的连接 关联区和内脏相关核团位于皮质下， 并在AD时经历严重的病理改变。第一个目标是 确定AD引起的病理改变是否有 偏爱特定的杏仁核。初始形态测量 分析试图确定阿尔茨海默病患者杏仁核萎缩是否与 随着神经元堆积密度的降低，神经元大小或神经元缩小 损失。神经炎性斑块(NPs)的地形分布和 神经原纤维缠结(NFT)将用硫黄素S来测试 认为某些杏仁核具有选择性易损性的假设 在公元后。杏仁核有严重、中等和可忽略的水平 将在超微结构水平上选择性地研究病理学 确定正常和病理改变之间的突触关系 结构，并确定突触长度和 突触密度与AD相关。第二个目标是确定 皮质和杏仁核投射神经元内NFT的关系 以及它们各自的几个终端字段中的NP。数据来自 包括海马区在内的颞叶皮质区域的形态计量分析 与杏仁核相关的结构和皮质下核团 将被用来测试跨神经元效应在脑血管疾病发病机制中的作用 广告。第三个目标是使用实验性神经解剖学技术。 探讨内源性神经元与阿尔茨海默病的关系 在化学定义的杏仁核神经元群体中。结构性的 本征神经元及其突触关系的底物将是 NADPH组织化学光镜和电子显微镜分析 抗生长抑素(SOM)和神经肽酪氨酸(NPY)抗血清。 这项研究的结果与广泛的基础和 临床神经科学研究。杏仁核在 边缘回路和这一回路的中断会导致虚弱 记忆力、注意力和情感方面的缺陷。这些研究的结果将 提供基本的定性和定量信息 在突触水平上理解结构-功能关系 正常老年人，以及神经性疾病，如 癫痫、阿尔茨海默氏症和帕金森氏症。