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; 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 Huntingtons病（HD）是一种无法治疗的遗传神经退行性疾病，导致运动和认知功能障碍和过早死亡，这是由于基底神经节中特定神经元的丧失。该项目具有访问HD的第一个转基因大鼠模型，将对症状前和有症状的大鼠的大脑中的神经网络变化进行第一项深入调查。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用于解决有关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度增强的体外高分辨率磁共振成像（MRI）（MRI）和扩散加权成像（DWI）与免疫细胞化学化学和组织学分析结合使用，并量化与观察到的行为改变一起进行的主要结构大脑变化和观察到的行为改变。其次，我们将使用顺行和逆行轴突跟踪技术组合在基底神经神经回路中发生变化。第三，我们将评估DWI作为检测该高清大鼠模型中轴突投影丢失的诊断工具。为了促进跨动物和实验的多模式数据的比较，将构建基底神经节的局部坐标系。该坐标系将有助于在共同框架中标准化和共同批准所有数据，适用于3D大脑图集环境中数据的未来共享。该项目将提供有价值的解剖学数据，这些数据与随后研究HD病理生理学和潜在治疗干预措施的评估有关。