Molecular mechanisms underlying BDNF-regulated dendrite branching

BDNF 调节树突分支的分子机制

• 批准号: 0919747
• 负责人: Bonnie Firestein
• 金额: $ 45万
• 依托单位: Rutgers University New Brunswick
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0919747&HistoricalAwards=false
• 关键词: Molecular; mechanisms; underlying; BDNF; regulated

For proper neuronal function to occur, the neuron must have the correct number of input centers, or dendrites, which look like branches on a tree. However, very little is currently known about how the pattern of these branches is determined. The goal of this project is to identify how both global and local changes in dendrite branching occurs. The Principal Investigator and her students will make use of molecular biology, biochemistry, and neuronal cell culture to study signaling by brain-derived neurotrophic factor (BDNF), a major regulator of dendrite branching. First, they will assess how administration of BDNF to neurons changes the shape of the dendrites overall and at distinct regions from the cell body. Second, neurons will be exposed to BDNF-coated latex beads to mimic local stimulation, and changes in the dendrite branching by this treatment will be compared to those that occur with global BDNF treatment. Third, they will use drugs and molecular techniques to identify the proteins that are responsible for the effects of BDNF. These studies are important because they will provide information on how dendrite branching is regulated during development to yield a functional brain. The impact of this research is far-reaching. Conducting the experiments will not only advance our understanding of how dendrite morphology is regulated but will also be part of a program to train high school, undergraduate, and graduate students in cutting-edge techniques in neuroscience. The project involves setting up an exchange program for undergraduate and Masters students at the University of Liberia so that they can perform summer research in the Firestein laboratory. A major goal is to establish an international program to bring neuroscience to the University of Liberia community through seminars, workshops, and exchange programs. This program will help educate people in a country facing global conflict.

为了使正常的神经元功能发生，神经元必须有正确数量的输入中心或树突，树突看起来像树上的树枝。然而，目前对这些分支的模式是如何确定的知之甚少。该项目的目标是确定树突分支的全局和局部变化是如何发生的。首席研究员和她的学生将利用分子生物学、生物化学和神经元细胞培养来研究脑源性神经营养因子（BDNF）的信号传导，BDNF是树突分支的主要调节因子。首先，他们将评估给神经元注入BDNF如何改变树突的整体形状和细胞体不同区域的形状。其次，将神经元暴露于BDNF涂层的乳胶珠中以模拟局部刺激，并将这种处理与BDNF全局处理的树突分支变化进行比较。第三，他们将使用药物和分子技术来识别负责BDNF作用的蛋白质。这些研究很重要，因为它们将提供在发育过程中如何调节树突分支以产生功能性大脑的信息。这项研究的影响是深远的。进行这些实验不仅将促进我们对树突形态是如何调节的理解，而且还将成为培养高中生、本科生和研究生神经科学前沿技术项目的一部分。该项目包括为利比里亚大学的本科生和硕士生设立一个交换项目，使他们能够在费尔斯坦实验室进行夏季研究。一个主要目标是建立一个国际计划，通过研讨会、讲习班和交换计划将神经科学带到利比里亚大学社区。这个项目将帮助教育面临全球冲突的国家的人民。