BRAIN STRUCTURE AND FUNCTION

在许多哺乳动物中，包括人类和一些非人类灵长类动物，衰老的大脑经历了一个 许多大规模的变化，可以观察到与成像和认知的方法。这些与年龄有关的 变化包括结构性萎缩、矿物质沉积增加、神经递质下降 生产，室周缺血，葡萄糖代谢下降（以及伴随的某些高血糖的下降）， 认知功能，特别是在记忆、认知速度和执行功能领域）。的 饮食限制（DR）对许多物种延长寿命的巨大影响及其对人类健康的有益影响 代谢过程，如氧化应激，表明这种干预也可能对大脑有好处。在 在这个项目中，我们提出了一个假设，即恒河猴经历慢性DR后， 明显的年龄相关的脑结构和功能的变化，比他们的自由进食年龄匹配 对照我们建议使用高分辨率的体积和微观结构的磁性测试这一假设 脑共振成像（MRI）技术和认知测试。我们的重点是结构和 认知功能可能会随着年龄的增长而改变。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， 如区域灰质和白色物质体积、T2弛豫时间（灰质矿化）、磁化强度 转移和扩散张量成像（白色物质完整性）。2)确定是否存在认知差异 使用计算机化的非人类灵长类动物行为范例， 以前被证明对年龄敏感。3)确定结构变化的速度是否 在DR组中减慢。这些目标将通过利用以下机构的专门知识和优秀资源来实现： 威斯康星州灵长类动物研究中心和凯克实验室的3特斯拉磁共振成像。分析将检查 基线和纵向差异。研究这些动物的独特机会， 全面的MRI成像和认知电池应提供急需的信息， 在大脑中的老化过程，并扩展DR干预的影响， 对人类来说意义重大。

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.