CHARACTERIZATION OF NEURAL NETWORK ALTERATIONS IN HUNTINGTON'S DISEASE MODEL

亨廷顿病模型中神经网络变化的表征

• 批准号: 8171575
• 负责人: TRYGVE LEERGAARD
• 金额: $ 0.55万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171575
• 关键词: Address; Affect; Animal Experiments; Atlases; Basal Ganglia; Behavioral; Biological Neural Networks; Brain; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Data; Diagnostic; Diffusion weighted imaging; Disease model; Environment; Evaluation; Functional disorder; Funding; Future; Genetic; Grant; Huntington Disease; Image; Impaired cognition; In Vitro; Inherited; Institution; Investigation; Magnetic Resonance Imaging; Modeling; Motor; Neuroanatomy; Neurodegenerative Disorders; Neurons; Rattus; Research; Research Personnel; Resolution; Resources; Source; Surveys; System; Techniques; Therapeutic Intervention; Transgenic Organisms; United States National Institutes of Health; data sharing; immunocytochemistry; neural circuit; premature; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Huntingtons Disease (HD) is an untreatable inherited neurodegenerative disease causing motor and cognitive dysfunction and premature death, due to loss of specific neurons in the basal ganglia. Having access to the first transgenic rat model of HD, this project will provide the 1st in-depth survey of neural network changes in the brains of pre-symptomatic and symptomatic rats. Expertise from neuroanatomy, genetics, and high-resolution tomographic imaging will be employed to address questions about how HD affects the neural circuitry of the basal ganglia. We will first localize and quantify major structural brain changes occurring in conjunction with observed behavioral alterations, using contrast-enhanced in vitro high-resolution magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) in combination with immunocytochemistry and histological analysis. Secondly, we will characterize alterations occurring in the basal ganglia neural circuits using combined anterograde and retrograde axonal tracing techniques. Third, we will evaluate DWI as a diagnostic tool for detecting loss of axonal projections in this HD rat model. To facilitate comparison of multi-modal data across animals and experiments, a local coordinate system for the basal ganglia will be constructed. This coordinate system will serve to normalize and co-register all data in a common framework, suitable for future sharing of data in a 3D brain atlas environment. The project will provide valuable anatomical data relevant for subsequent investigations of HD pathophysiology and evaluation of potential therapeutic interventions.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 亨廷顿病 (HD) 是一种无法治疗的遗传性神经退行性疾病，由于基底神经节中特定神经元的缺失，导致运动和认知功能障碍以及过早死亡。通过获得第一个 HD 转基因大鼠模型，该项目将首次深入研究症状前和症状大鼠大脑中的神经网络变化。来自神经解剖学、遗传学和高分辨率断层扫描成像的专业知识将被用来解决有关 HD 如何影响基底神经节神经回路的问题。我们将首先使用对比增强的体外高分辨率磁共振成像（MRI）和扩散加权成像（DWI）结合免疫细胞化学和组织学分析来定位和量化与观察到的行为改变相关的主要大脑结构变化。其次，我们将使用组合的顺行和逆行轴突追踪技术来表征基底节神经回路中发生的改变。第三，我们将评估 DWI 作为检测 HD 大鼠模型中轴突投影缺失的诊断工具。为了便于比较动物和实验的多模态数据，将构建基底神经节的局部坐标系。该坐标系将用于在通用框架中标准化和共同注册所有数据，适合未来在 3D 大脑图谱环境中共享数据。该项目将为 HD 病理生理学的后续研究和潜在治疗干预的评估提供有价值的解剖数据。