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物种，老化的大脑经历了 通过成像和认知方法可以观察到的大范围变化的数量。这些与年龄有关的人 变化包括结构萎缩，矿物质沉积增加，神经递质下降 产生，脑室周围缺血，葡萄糖代谢下降(并伴随着某些较高的 认知功能，特别是在记忆、认知速度和执行功能领域)。这个 饮食限制(DR)对许多物种延长寿命的戏剧性影响及其对 氧化应激等代谢过程表明，这种干预可能对大脑也有好处。在……里面 在这个项目中，我们建议检验这样一种假设，即经历慢性DR的恒河猴表现出的症状较少 与年龄匹配的随意喂养相比，与年龄相关的大脑结构和功能显著变化 控制。我们建议使用高分辨率的体积和微结构磁性来检验这一假说 大脑的磁共振成像(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和对照动物在组织体积和完整性等方面是否存在基线差异 作为局部灰质和白质体积、T2弛豫时间(灰质矿化)、磁化强度 传递和扩散张量成像(白质完整性)。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式在DR组和对照组之间进行比较 以前被证明对年龄很敏感。3)确定结构变化的速度是否已经 在DR组中速度减慢。这些目标将利用的专业知识和优秀的资源 威斯康星州灵长类动物研究中心和凯克实验室的3-特斯拉核磁共振。分析将检查 基线和纵向差异分组。用一个独特的机会研究这些动物 全面的MRI成像和认知电池应该提供关于全球 大脑的衰老过程，并扩大对DR干预在以下领域的效果的评估 对人类意义重大。

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.