STRUCTURAL STUDIES IN THE CENTRAL NERVOUS SYSTEM

中枢神经系统的结构研究

• 批准号: 8245729
• 负责人: ALAN PETERS
• 金额: $ 29.67万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8245729
• 关键词: 19 year old; Affect; Age; Age of Onset; Age-associated memory impairment; Aging; Aging-Related Process; Alzheimer' s Disease; Antibodies; Area; Astrocytes; Attention; Autophagosome; Axon; Basal lamina; Behavioral; Beryllium; Biological Preservation; Blood - brain barrier anatomy; Blood capillaries; Brain; Brain Part; Brain region; Capillary Endothelial Cell; Cells; Cerebral cortex; Cerebral hemisphere; Cleaved cell; Cognitive; Cognitive aging; Connective Tissue; Cytoplasm; Data; Dendrites; Dendritic Spines; Deposition; Digestion; Dorsal; Electrolytes; Electron Microscopy; Electrons; Endothelial Cells; Excitatory Synapse; Exhibits; Failure; Fiber; Goals; Grant; Immune response; Impaired cognition; Inflammation; Inhibitory Synapse; Label; Left; Liquid substance; Longevity; Lysosomes; Magnetic Resonance Imaging; Measures; Memory; Microglia; Microscopic; Monkeys; Morphology; Myelin; Myelin Sheath; Myelinated nerve fiber; Neocortex; Nerve Degeneration; Nerve Fibers; Nervous system structure; Neuraxis; Neurites; Neurofibrillary Tangles; Neuroglia; Neurons; Oligodendroglia; Organelles; Oxidative Stress; Parietal; Pathway interactions; Peptides; Phagocytosis; Phagosomes; Phase; Physiological; Plastics; Population; Prefrontal Cortex; Primates; Property; Prosencephalon; Proteins; Pyramidal Cells; Rattus; Reporting; Severities; Signal Transduction; Site; Source; Structure; Structure of genu of corpus callosum; Suggestion; Synapses; System; Testing; Time; Tissues; Ubiquitin; Ubiquitinated Protein Degradation; Vertebral column; Visual Cortex; Work; age effect; age related; aging brain; area striata; base; capillary; density; executive function; extrastriate visual cortex; frontal lobe; human tissue; interest; light microscopy; macromolecule; middle age; multicatalytic endopeptidase complex; myelin degeneration; neocortical; neuroimaging; neuron loss; neuronal excitability; normal aging; programs; relating to nervous system; small molecule; tau Proteins; white matter

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.

该项目的目标是描述与衰老相关的大脑结构变化 认知障碍。衰老大脑最显着的变化包括髓鞘质和 神经胶质细胞的变化，而神经元的变化则更为微妙。拟议的研究建立在重要的基础上 研究结果表明，与年龄相关的认知障碍可能代表轴突传导的失败 对记忆和执行功能至关重要的通路和大脑区域。有五个目标：1） 中年猴子（13-19岁）大脑中有髓神经纤维的结构将是 研究以确定哪些退行性变化首先发生，以及这些变化是否先于发生 的认知障碍。 2）检查前额皮质纤维通路的超微结构 整个生命周期，因为这是与年龄相关的认知障碍有关的皮质区域。背部 纵向束将成为一个特别的焦点，因为它似乎随着年龄的增长而受损（通过测量） 神经影像学研究。 3）将评估老化新皮质的神经退行性变化，包括 前额叶区域 8a，据报道该区域神经元丢失。神经元受损的机制 还将使用泛素抗体来研究被消除的元件，并且突触数量将被 研究了前额叶区域 46 和视觉区域 17 的第 2/3 层和第 5 层，以确定是否发生变化 对称和不对称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) 将在区域 46 和 17 中对神经胶质细胞群进行定量检查 年龄和认知状态。 5) 检查血脑屏障的超微结构以确定 退行性变化是否可能允许分子进入大脑从而损害神经元及其轴突 在老化过程中。该项目的研究将提供有关结构的关键信息 大脑老化，并将突出那些可能导致认知能力下降的变化。