STRUCTURAL STUDIES IN THE CENTRAL NERVOUS SYSTEM

这个项目的目标是描述老化大脑的结构变化，这些变化与 认知障碍。大脑老化中最显著的变化包括髓鞘和 神经胶质细胞，而神经元的变化则更为微妙。拟议的研究建立在重要的 研究结果提示，与年龄相关的认知障碍可能代表着轴突传导的失败 对记忆和执行功能至关重要的通路和大脑区域。它有五个目标：1) 中年猴(13-19岁)脑内有髓神经纤维的结构 研究以确定哪些退行性变化最先发生，以及这些变化是否先于发病 认知障碍的症状。2)前额叶皮质纤维通路的超微结构 整个寿命，因为这是与年龄相关的认知障碍有关的皮质区域。背部 纵束将是一个特别的焦点，因为它似乎随着年龄的增长而受损，通过 神经成像研究。3)将评估老化新皮质的神经退行性变化，包括 前额叶8a区，已有神经元丢失的报道。损伤神经元的机制 消除的元件也将使用泛素抗体进行调查，突触数量将 在前额叶区域46和视觉区域17的第2/3层和第5层进行研究以确定 对称性和非对称性突触可以解释所描述的与年龄相关的神经元兴奋性变化 根据项目3.4)，将对46和17区的神经胶质细胞群进行定量检查 年龄和认知状况。5)检查血脑屏障的超微结构以确定 退行性改变是否可能允许分子进入大脑，从而破坏神经元及其轴突 在老化过程中。这个项目中的研究将提供关于 大脑老化，并将突出那些可能导致认知能力下降的变化。

The goal of this project is to describe the structural changes in the aging brain that are associated with cognitive impairment. The most prominent changes in the aging brain include abnormalities in myelin and neuroglial cells, while the changes in neurons are more subtle. The proposed studies build on significant findings suggesting that age-related cognitive impairment may represent a failure of axonal conduction in pathways and brain regions that are critical for memory and executive function. There are five aims: 1) The structure of myelinated nerve fibers in the brain of middle aged monkeys (13 - 19 years of age) will be studied to determine which degenerative changes occur first, and whether these changes precede the onset of cognitive impairment. 2) The ultrastructure of the fiber pathways in the prefrontal cortex will be examined across the lifespan since this is the cortical region implicated in age-related cognitive impairment. The dorsal longitudinal fasciculus will be a particular focus because it appears to be damaged with age as measured by neuroimaging studies. 3) The neurodegenerative changes in the aging neocortex will be assessed, including prefrontal area 8a, where neuron loss has been reported. The mechanism by which damaged neuronal elements are eliminated will also be investigated using antibodies to ubiquitin, and synapse number will be studied in layers 2/3 and layer 5 of prefrontal area 46 and visual area 17 to determine whether changes in symmetric and asymmetric synapses can explain the age-related changes in neuronal excitability described by Project 3. 4) The neuroglial cell population will be examined quantitatively in areas 46 and 17 in relation to age and cognitive status. 5) The ultrastructure of the blood brain barrier will be examined to determine whether degenerative changes might allow molecules into the brain which damage neurons and their axons during the aging process. The studies in this project will provide critical information about the structure of the aging brain and will highlight those changes that may be responsible for cognitive decline.