MRI and mouse models of Alzheimer's disease and aging

阿尔茨海默病和衰老的 MRI 和小鼠模型

• 批准号: 7009921
• 负责人: SCOTT A SMALL
• 金额: $ 30.59万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7009921
• 关键词: Alzheimer' s disease; aging; bioimaging /biomedical imaging; blood volume; brain electrical activity; brain imaging /visualization /scanning; brain metabolism; cerebrum; cytochrome oxidase; disease /disorder model; enzyme activity; genetically modified animals; hippocampus; histochemistry /cytochemistry; laboratory mouse; magnetic resonance imaging; neuropharmacology; pathologic process

DESCRIPTION (provided by applicant): A range of studies suggests that Alzheimer's disease (AD) begins by impairing synaptic function in select subregions of the hippocampal formation. Detecting synaptic dysfunction with anatomical precision has emerged as an important goal, both to improve our diagnostic abilities and for the purposes of drug development. Synaptic dysfunction typically affects basal brain metabolism. Among the hemodynamic correlates of brain metabolism that can be assessed with magnetic resonance imaging (MRI), cerebral blood volume (CBV) is the one that can most readily visualize individual hippocampal subregions. The first goal of this proposal is to determine whether high-resolution measures of CBV do in fact reflect underlying physiology and metabolism, and whether it can detect AD-related and age-related neuronal dysfunction. The second goal is to confirm that AD-related and age-related hippocampal dysfunction target separate hippocampal subregions. The third goal is to demonstrate that CBV measures can reliably detect the effect of a pharmacological intervention, thereby testing whether this approach can be used for drug development. Independent validation of neuronal dysfunction requires invasive techniques--such as ex vivo slice electrophysiology and in vitro histochemistry-- and therefore these goals can only be achieved in experimental animals. Here we focus on mice because they are the only species that provide both a model of AD and a model of normal aging. Furthermore, because of their relatively short life span, we can follow mice longitudinally, thereby mapping the temporal as well as spatial pattern of dysfunction. With these advantages in mind, we have constructed an MRI laboratory tailored exclusively to mouse MRI, and have optimized CBV approaches for subregional analysis of the hippocampus.

描述（由申请人提供）：一系列研究表明，阿尔茨海默氏病（AD）始于损害海马结构选定亚区域的突触功能。以解剖精度检测突触功能障碍已成为一个重要目标，既可以提高我们的诊断能力，也可以用于药物开发的目的。突触功能障碍通常会影响基础脑代谢。在可以通过磁共振成像 (MRI) 评估的脑代谢的血流动力学相关性中，脑血容量 (CBV) 是最容易可视化单个海马分区的一项。 该提案的第一个目标是确定 CBV 的高分辨率测量是否确实反映了潜在的生理和代谢，以及它是否可以检测 AD 相关和年龄相关的神经元功能障碍。第二个目标是确认 AD 相关和年龄相关的海马功能障碍针对不同的海马亚区域。第三个目标是证明 CBV 测量可以可靠地检测药物干预的效果，从而测试这种方法是否可以用于药物开发。 对神经元功能障碍的独立验证需要侵入性技术，例如离体切片电生理学和体外组织化学，因此这些目标只能在实验动物中实现。在这里，我们关注小鼠，因为它们是唯一同时提供 AD 模型和正常衰老模型的物种。此外，由于它们的寿命相对较短，我们可以纵向跟踪小鼠，从而绘制功能障碍的时间和空间模式。考虑到这些优势，我们建立了专门针对小鼠 MRI 的 MRI 实验室，并优化了用于海马分区分析的 CBV 方法。