ApoE and cytokines: In vivo effects on AD-like pathology

ApoE 和细胞因子：对 AD 样病理的体内影响

• 批准号: 7157878
• 负责人: JESSICA KOENIGSKNECHT-TALBOO
• 金额: $ 5.65万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157878
• 关键词: Alzheimer' s disease; amyloid proteins; apolipoprotein E; bioimaging /biomedical imaging; cell cell interaction; cell motility; cellular pathology; cytokine; dendrites; fluorescence microscopy; genetically modified animals; green fluorescent proteins; image processing; imaging /visualization /scanning; laboratory mouse; microglia; morphometry; neurons; postdoctoral investigator; protein protein interaction

DESCRIPTION (provided by applicant): In order to fully appreciate events that occur during Alzheimer's disease (AD) pathogenesis it is critical to understand the relationships between the various cell types and molecules involved and the pathological hallmarks of the disease. One way to better understand these complex relationships is to visualize them in vivo, in real time, while blocking or augmenting the function of particular molecules that are potentially involved in these relationships. To this end, we propose to use in vivo multiphoton imaging of a murine brain containing AD- like pathology to visualize interactions between microglia, neurons, and neuronal processes in real time. This will enable us to determine how specific molecules present within the milieu of the AD brain affect the structure and function of these cell types. We hypothesize that the interaction between apoE and aggregated beta-amyloid is dynamic and regulates microglial motility and cytokine release that results in ongoing injury to neuronal processes. Elucidation of how microglial cell morphology and motility as well as neuronal injury are affected by aggregated beta-amyloid, apoE and specific cytokines produced by microglia will be explored in vivo.

描述（由申请人提供）：为了充分理解阿尔茨海默氏病（AD）发病机理中发生的事件，了解各种细胞类型和涉及的分子与疾病的病理标志之间的关系至关重要。更好地理解这些复杂关系的一种方法是实时在体内可视化它们，同时阻止或增强潜在参与这些关系的特定分子的功能。为此，我们建议使用含有AD类病理学的鼠大脑中的体内多光子成像，以实时可视化小胶质细胞，神经元和神经元过程之间的相互作用。这将使我们能够确定广告大脑环境中的特定分子如何影响这些细胞类型的结构和功能。我们假设APOE与聚集的β-淀粉样蛋白之间的相互作用是动态的，并且调节小胶质细胞运动性和细胞因子释放，从而导致神经元过程持续损伤。将在体内探索小胶质细胞的形态和运动性以及神经元损伤如何受到小胶质细胞产生的特定细胞因子的影响。