BIOCHEMICAL STUDIES OF INFLAMMATORY MEDIATORS AND DYSMYELINATION

炎症介质和髓鞘脱失的生化研究

• 批准号: 8365559
• 负责人: CARMELA R ABRAHAM
• 金额: $ 0.23万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-08-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8365559
• 关键词: Action Potentials; Age; Age-associated memory impairment; Aging; Aldehydes; Axon; Biochemical; Biological Markers; Biological Preservation; Biology; Blood; Blood specimen; Brain; Cognitive; Collection; Electron Microscopy; Funding; Grant; Human; Impaired cognition; Inflammation; Inflammation Mediators; MRI Scans; Macaca mulatta; Mass Spectrum Analysis; Medicine; Modeling; Monkeys; National Center for Research Resources; Neurons; Perfusion; Principal Investigator; Process; Proteins; Research; Research Infrastructure; Resources; Sampling; Source; Staging; Structure; Testing; United States National Institutes of Health; behavior test; brain tissue; cohort; cost; dysmyelination; in vivo; middle age; multidisciplinary; neurophysiology; sample fixation; tissue fixing; white matter

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The rhesus monkey is a model of normal human aging that enables cognitive testing to be followed by optimal preservation of brain tissue for multidisciplinary studies. These ongoing studies test the hypothesis that age-related cognitive decline results from a cascade of mild degenerative changes beginning in early middle age with inflammation and damage in white matter that leads to functional changes in axons and progresses to functional and structural changes in neurons. Three cohorts of monkeys are being studied to test various aspects of this hypothesis. After behavioral testing of the first cohort, MRI scans are followed by in vivo neurophysiology and perfusion fixation to provide fresh and fixed tissue to identify brain changes underlying cognitive decline. A second cohort of 6 middle aged monkeys is being treated like cohort 1 except their samples will be perfusion fixed with mixed aldehydes for electron microscopy to supplement existing samples and allow identification of the ultrastructural changes. A third cohort of 12 early middle aged monkeys (ages 13-15) is being followed longitudinally for with repeated behavioral testing, MRI scans of the brain, and analysis of blood and CSF. Longitudinal MRIs will reveal concurrent changes in the in vivo brain structure, and CSF and blood samples will allow biomarkers to be followed. For cohorts 1 and 3, perfusion fixation is preceded by in vivo neurophysiological assessment of compound action potentials. Two stage perfusion follows to allow immediate collection of unfixed samples from one hemisphere before the remainder of the brain is fixed. Fixed tissue is used for anatomical studies, including stereological studies of neuron numbers and immunocytochemical studies of inflammation and other degenerative processes. Structures of key proteins are being determined by FTMS and LC-MS/MS.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 恒河猴是正常人衰老的模型，可以使认知测试在多学科研究中最佳保留脑组织。这些正在进行的研究检验了与年龄相关的认知下降的假设是由于中期早期的级联变化而导致的，随着炎症和白质的损害，这会导致轴突的功能变化，并发展为神经元的功能和结构变化。正在研究三只猴子，以检验该假设的各个方面。在对第一个队列的行为测试之后，MRI扫描之后是体内神经生理学和灌注固定，以提供新鲜和固定的组织，以识别认知能力下降的大脑变化。第二个组的6个中年猴子被视为同类1，除了它们的样品将用混合醛固定在电子显微镜中，以补充现有样品，并允许鉴定超微结构的变化。第三个组的12名中年早年猴子（13-15岁）进行了纵向，以重复进行行为测试，大脑的MRI扫描以及对血液和CSF的分析。纵向MRIS将揭示体内大脑结构的同时变化，CSF和血液样本将允许遵循生物标志物。对于队列1和3，灌注固定之前是对复合作用电位的体内神经生理学评估。在固定剩余的大脑之前，两个阶段的灌注允许立即从一个半球收集未固定的样品。固定组织用于解剖学研究，包括对炎症和其他退化过程的神经元数量和免疫细胞化学研究的立体研究。关键蛋白的结构由FTM和LC-MS/MS确定。