Astrocyte remodeling during the sleep/wake cycle

睡眠/觉醒周期期间星形胶质细胞的重塑

• 批准号: 9374291
• 负责人: Annalisa Scimemi
• 金额: $ 7.3万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT ALBANY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9374291
• 关键词: Affect; Alzheimer' s Disease; Anatomy; Astrocytes; Brain; Brain Diseases; Brain region; Cells; Chronic; Circadian Rhythms; Dehydration; Development; Diffusion; Disease; Excitatory Synapse; Extracellular Space; Face; Glutamate Transporter; Glutamates; Goals; Health; Hippocampus (Brain); Hypothalamic structure; Impairment; Investigation; Knowledge; Lactation; Life; Maps; Membrane Proteins; Microscopy; Mission; Molecular; Morphology; Mus; Neurodegenerative Disorders; Neurons; Neuropil; Neurotransmitters; Phase; Pilot Projects; Plasticizers; Presynaptic Terminals; Process; Public Health; Research; Resolution; Series; Sleep; Sleep Wake Cycle; Structure; Synapses; Synaptic Transmission; Techniques; Testing; Time; United States National Institutes of Health; cognitive ability; cognitive skill; density; experimental study; functional plasticity; high resolution imaging; innovation; novel; prevent; programs; reconstruction; suprachiasmatic nucleus; three-dimensional modeling; tool; transmission process; uptake

PROJECT SUMMARY The brain is plastic and is built for changes in its structure and function. Structural and functional plas- ticity have been the subject of intense investigation, but whether similar phenomena occur also in astro- cytes remains enigmatic. The reason for this noticeable gap of knowledge is that until recently, we lacked microscopy approaches that can provide both a high-resolution image of astrocytic processes and a full description of the morphology of entire astrocytes. Expansion microscopy can challenge this status quo by providing an exciting new way to analyze the structure of astrocytes and the distribution of membrane proteins. The overall objective is to determine how the morphology of astrocytes and the sub-cellular distribution of glutamate transporters changes during the sleep/wake cycle. Our central hy- pothesis is that astrocytic processes move away from excitatory synapses during the sleep phase, al- tering glutamate diffusion and weakening excitatory synaptic transmission in the brain. We plan to test our central hypothesis and attain the objective of this application by pursuing the following specific aims: (1) determine the effect of the sleep/wake cycle on astrocyte morphology; (2) map the molecular distribution of glutamate transporters in astrocytes during the sleep/wake cycle; (3) develop 3D models of glutamate diffusion and excitatory transmission during the sleep/wake cycle. The proposed research is significant because it may generate groundbreaking information on how changes in the structure and function of astrocytes contribute to the onset of neurodegenerative diseases. The proposed research is innovative because it aims to develop a new and comprehensive toolbox to investigate fundamental mechanisms regulating the function of the brain. Ultimately, these findings are expected to have an im- portant positive impact in the delineation of the molecular and cellular mechanisms underlying our cog- nitive abilities during health and disease.

项目概要 大脑是可塑的，是为了改变其结构和功能而构建的。结构和功能塑料 稠度一直是深入研究的主题，但类似的现象是否也发生在天体中 细胞仍然是个谜。造成这种明显知识差距的原因是，直到最近，我们 缺乏可以提供星形胶质细胞过程的高分辨率图像的显微镜方法 以及整个星形胶质细胞形态的完整描述。膨胀显微镜可以挑战这一点 通过提供一种令人兴奋的新方法来分析星形胶质细胞的结构和分布来改变现状 膜蛋白。总体目标是确定星形胶质细胞的形态和 谷氨酸转运蛋白的亚细胞分布在睡眠/觉醒周期中发生变化。我们的中央hy- 假设星形胶质细胞过程在睡眠阶段远离兴奋性突触，al- 阻止谷氨酸扩散并削弱大脑中的兴奋性突触传递。我们计划测试 我们的中心假设，并通过追求以下具体目标来实现本应用的目标 目的：（1）确定睡眠/觉醒周期对星形胶质细胞形态的影响； (2)分子图谱 睡眠/觉醒周期期间星形胶质细胞中谷氨酸转运蛋白的分布； (3)开发3D模型 睡眠/觉醒周期期间谷氨酸扩散和兴奋性传递的影响。拟议的研究 很重要，因为它可能会产生有关结构和结构如何变化的突破性信息 星形胶质细胞的功能有助于神经退行性疾病的发生。拟议的研究是 创新是因为它旨在开发一个新的综合工具箱来研究基本原理 调节大脑功能的机制。最终，这些发现预计将产生重大影响 对描绘我们认知背后的分子和细胞机制产生重要的积极影响 健康和疾病期间的原始能力。