BRAIN STRUCTURE AND FUNCTION

大脑结构和功能

• 批准号: 7041058
• 负责人: Sterling C Johnson
• 金额: $ 16.01万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7041058
• 关键词: Macaca mulatta; aging; animal developmental psychology; biological models; brain mapping; brain morphology; cognition; developmental neurobiology; developmental nutrition; dietary restriction; gray matter; longitudinal animal study; magnetic resonance imaging; neural degeneration; nutrition related tag; psychological aspect of aging; psychological tests; psychomotor function; short term memory; white matter

In many mammals, including humans and some non-human primate species, the aging brain undergoes a number of large-scale changes that can be observed with imaging and cognitive approaches. These agerelated changes include structural atrophy, increased mineral deposition, decline in neurotransmitter production, periventricular ischemia, decline in glucose metabolism (and concomitant decline in certain higher cognitive functions, particularly in the domains of memory, cognitive speed, and executive function). The dramatic effect of diet restriction (DR) to increase lifespan in many species and its salutary effects on metabolic processes such as oxidative stress, suggest that this intervention may also be good for the brain. In this project, we propose to test the hypothesis that rhesus monkeys undergoing chronic DR will exhibit less pronounced age-related brain structural and functional changes than their ad libitum fed age-matched controls. We propose to test this hypothesis using high-resolution volumetric and microstructural Magnetic Resonance Imaging (MRI) techniques of the brain and cognitive tests. Our emphasis is on structures and cognitive functions that may change with age. We plan to accomplish the following specific aims: 1) determine if baseline differences exist between DR and control animals on tissue volume and integrity such as regional gray and white matter volume, T2 relaxation time (gray matter mineralization), magnetization transfer, and diffusion tensor imaging (white matter integrity). 2) determine whether cognitive differences exist between DR and control groups using computerized non-human primate behavioral paradigms that have previously been shown to be sensitive to age. 3) determine whether the rate of structural change has been slowed in the DR group. These aims will be accomplished utilizing the expertise and excellent resources of the Wisconsin Primate Research Center and the Keck Laboratory's 3-Tesla MRI. Analyses will examine the groups for baseline and longitudinal differences. The unique opportunity to study these animals with a comprehensive MRI imaging and cognitive battery should provide much needed information regarding global aging processes in the brain, and extend the evaluation of the effects of the DR intervention in domains of great significance to humans.

在许多哺乳动物中，包括人类和一些非人类灵长类动物，衰老的大脑会经历 通过成像和认知方法可以观察到的大规模变化的数量。这些与年龄有关的 变化包括结构萎缩、矿物质沉积增加、神经递质下降 生产、脑室周围缺血、葡萄糖代谢下降（以及伴随的某些较高水平的下降） 认知功能，特别是在记忆、认知速度和执行功能领域）。这 饮食限制（DR）对延长许多物种的寿命具有显着效果，及其对人类的有益影响 氧化应激等代谢过程表明这种干预也可能对大脑有益。在 在这个项目中，我们建议测试以下假设：患有慢性 DR 的恒河猴会表现出较少的症状 与年龄相匹配的随意进食相比，与年龄相关的大脑结构和功能发生了明显的变化 控制。我们建议使用高分辨率体积和微观结构磁性来测试这一假设 大脑共振成像 (MRI) 技术和认知测试。我们的重点是结构和 认知功能可能随年龄而变化。我们计划实现以下具体目标：1） 确定 DR 和对照动物之间在组织体积和完整性方面是否存在基线差异，例如 作为区域灰质和白质体积、T2 弛豫时间（灰质矿化）、磁化强度 转移和扩散张量成像（白质完整性）。 2）判断是否存在认知差异 使用计算机化的非人类灵长类动物行为范式在 DR 组和对照组之间进行 此前已被证明对年龄敏感。 3）确定结构变化率是否已 DR 组减慢。这些目标将利用以下机构的专业知识和优质资源来实现： 威斯康星灵长类动物研究中心和凯克实验室的 3-特斯拉 MRI。分析将检查 基线和纵向差异的分组。研究这些动物的独特机会 全面的 MRI 成像和认知电池应该提供有关全球的急需信息 大脑的衰老过程，并将 DR 干预的效果评估扩展到以下领域： 对人类具有重大意义。