Nano-Scale Processes of Dendrogenesis

树突发生的纳米级过程

基本信息

批准号：
7740046
负责人：
Martha U Gillette
金额：
$ 23.78万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7740046
关键词：
Actins Address Advanced Development Aging Alzheimer&apos s Disease Analytical Chemistry Architecture Arts Behavior Binding Biological Brain Brain Diseases Cells Chemicals Complex Cues Defect Dendrites Dendritic Spines Development Devices Disease Engineering Environment Environmental Risk Factor Filopodia Generations Goals Growth Hippocampus (Brain)Image In Vitro Individual Length Mental Health Methods Microfluidics Microscopy Modeling Monitor Morphogenesis Nanotechnology Nervous system structure Neurites Neurons Neurosciences Optics Parkinson Disease Pattern Physical environment Physiologic pulse Population Positioning Attribute Process Property Rattus Rest Role Sampling Schizophrenia Science Shapes Signal Transduction Signaling Molecule Site Solutions Stimulus Structure Surface Synapses System Three-Dimensional Image Time Transgenic Mice Vertebral column Width Work age related chemical binding density depression design economic cost experience imprint improved information processing innovation insight nanolitre nanoscale neuron development novel presynaptic programs public health relevance relating to nervous system repaired research study response restoration success tool

项目摘要

DESCRIPTION (provided by applicant): Proper wiring of the nervous system requires interplay of intrinsic and extrinsic signals that shape neurite development, architecture and function. Whereas axonal development is relatively well understood, less is known of the forces that shape dendrites, especially the nano-scale filopodia that decorate developing dendritic shafts. What factors influence dendritic filopodia during wiring of brain circuits? Do filopodia contribute to formation of dendritic spines, sites of synaptic information processing and plasticity? We hypothesize that chemical cues in substrate-bound gradients instruct dendrite morphogenesis and maturation via nanometer-scale changes that transform collateral filopodia into spines. We will build upon our recent success in culturing hippocampal neurons from early post-natal rat at very low densities in refined microfluidic environments. Centered in neuroscience, this R21 proposal bridges with materials science to create and exploit complex gradient chemical fields-ones embedding nanometer scale design rules and capable of imprinting the physical environments of neurons in culture with specific immobilized and diffusive factors. These experimental competencies are provided by state-of-the-art microfluidic systems that exploit a variety of physical behaviors to actuate programmed chemo-temporal profiles within the device. Specific aims are to: 1) characterize collateral filopodial behavior in response to 2D surface gradients of bioactive molecules, and 2) build upon these findings to construct 3D gradient environments that encourage filopodial differentiation and enable responses to diffusive stimuli. Models are hippocampal neurons of early post-natal rat and EGFP-actin transgenic mouse. We seek to discover novel insights, solutions and applications that impact mental health, neural repair and restoration of function. The intransigence of brain disorders and damage to treatment is of rising concern as many incurable conditions (schizophrenia, depression, Parkinson's and Alzheimer's disease) have huge economic costs and will increase with the aging of our population. PUBLIC HEALTH RELEVANCE: Nano-scale Processes of Dendrogenesis Proper wiring of the nervous system requires interplay of intrinsic and extrinsic signals that shape neurite development, architecture and function. This proposal seeks to understand the role of nano-scale filopodia in hippocampal dendrogenesis and spine formation by bridging neuroscience with materials science to create and exploit complex gradient chemical fields embedding nanometer-scale design features in nanoliter physical environments. This innovative approach positions us to discover novel insights for normal dendritic spine formation that will offer new strategies, solutions and applications that impact mental health, neural repair and restoration of function, which are of rising concern as many incurable conditions (schizophrenia, depression, Parkinson's and Alzheimer's disease) have huge economic costs and will increase with the aging of our population.

描述（由申请人提供）：神经系统的正确接线需要塑造神经突发育，建筑和功能的内在和外在信号的相互作用。尽管轴突发育的理解相对较好，但对塑造树突的力，尤其是装饰开发树突状轴的纳米尺度丝状虫的力量。哪些因素会影响脑电路接线期间的树突状丝状虫？丝状虫是否有助于形成树突状刺，突触信息处理的部位和可塑性？我们假设底物结合梯度中的化学提示通过纳米尺度的变化指导树突形态发生和成熟，从而将侧支丝霉素转化为脊柱。我们将基于我们最近在高产后大鼠培养海马神经元的成功基础，在精制的微流体环境中，密度非常低。该R21提案桥梁与材料科学桥梁以神经科学为中心，以创建和利用复杂的梯度化学场嵌入纳米尺度设计规则，并能够用特定的固定和扩散因素将神经元的物理环境印记。这些实验能力是由最先进的微流体系统提供的，这些系统利用各种物理行为在设备中启动了程序化的化学速率。具体目的是：1）响应生物活性分子的二维表面梯度而表征附带丝源行为，而2）建立在这些发现的基础上，以构建3D梯度环境，以鼓励丝状分化并促进对扩散刺激的响应。模型是早期产后大鼠和EGFP-肌动蛋白转基因小鼠的海马神经元。我们试图发现影响心理健康，神经修复和功能恢复的新颖见解，解决方案和应用。由于许多无法治愈的疾病（精神分裂症，抑郁症，帕金森氏症和阿尔茨海默氏病）的不断增长，脑部疾病的不适和治疗损害的经济成本很大，并且随着我们人口的衰老而增加。公共卫生相关性：神经系统的纳米级过程适当接线需要塑造神经突发育，建筑和功能的内在和外在信号相互作用。该建议旨在通过与材料科学桥接神经科学来创建和利用嵌入纳米属物理环境中的纳米尺度设计特征来创建和利用复杂的梯度化学领域，从而了解纳米级丝霉素在海马树突形成和脊柱形成中的作用。这种创新的方法使我们对正常的树突状脊柱形成的新颖见解进行了定位，这些新见解将提供新的策略，解决方案和应用，影响心理健康，神经修复和功能的恢复，这是令人关注的问题（精神分裂症，抑郁症，帕金森氏症，帕金森氏症和阿尔茨海默氏病），这会增加我们的经济成本，并会随着我们的数量而增加。