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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）：神经系统的正确布线需要形成神经突发育、结构和功能的内在和外在信号的相互作用。虽然轴突的发展是相对较好的理解，很少有人知道的力量，形状树突，特别是纳米级的丝状伪足装饰发展树突轴。什么因素影响树突状丝状伪足在布线的大脑回路？丝状伪足是否有助于树突棘的形成，突触信息处理和可塑性的位点？我们推测，化学线索在基板结合梯度指示树突形态发生和成熟，通过纳米尺度的变化，将侧丝状伪足成刺。我们将建立在我们最近的成功培养海马神经元从出生后早期大鼠在非常低的密度在精致的微流体环境。以神经科学为中心，这个R21建议与材料科学建立桥梁，以创建和利用复杂的梯度化学场-嵌入纳米级设计规则的化学场，并能够在具有特定固定和扩散因子的培养中压印神经元的物理环境。这些实验能力是由最先进的微流体系统提供的，该系统利用各种物理行为来驱动设备内的编程化学时间曲线。具体目标是：1）表征响应于生物活性分子的2D表面梯度的侧支丝状伪足行为，以及2）基于这些发现构建促进丝状伪足分化并能够响应扩散刺激的3D梯度环境。模型为出生后早期大鼠和EGFP-actin转基因小鼠海马神经元。我们寻求发现影响心理健康，神经修复和功能恢复的新见解，解决方案和应用程序。大脑疾病和损害对治疗的顽固性越来越令人关切，因为许多无法治愈的疾病（精神分裂症、抑郁症、帕金森病和阿尔茨海默病）具有巨大的经济成本，并将随着我们人口的老龄化而增加。公共卫生关系：神经系统的正确布线需要内在和外在信号的相互作用，这些信号塑造了神经突的发育、结构和功能。该提案旨在了解纳米级丝状伪足在海马树突发育和脊柱形成中的作用，方法是将神经科学与材料科学相结合，以创建和利用在纳升物理环境中嵌入纳米级设计特征的复杂梯度化学场。这种创新的方法使我们能够发现正常树突棘形成的新见解，这将提供影响心理健康，神经修复和功能恢复的新策略，解决方案和应用，这些问题越来越受到关注，因为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症）具有巨大的经济成本，并将随着我们人口的老龄化而增加。