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Imaging nerve growth factor signal transduction in live neurons

活神经元中神经生长因子信号转导的成像

基本信息

批准号：
7223656
负责人：
Bianxiao Cui
金额：
$ 5.75万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-12-01 至 2008-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7223656
关键词：
Alzheimer&apos s Disease Amyloid beta-Protein Precursor Atrophic Axon Axonal Transport Binding Brain C-terminal Cells Cholinergic Agents Chromosomes, Human, Pair 16 Color Defect Down Syndrome Endosomes Energy Supply Event Fluorescence Frequencies Genes Green Fluorescent Proteins Image Imaging Techniques Individual Label Lead Length Life Link Localized Location Maintenance Measures Microtubules Mitochondria Modeling Motor Movement Mus Nerve Growth Factors Neurons Neurotrophic Tyrosine Kinase Receptor Type 1 Numbers Pathogenesis Patients Pattern Presynaptic Terminals Protein Overexpression Proteins Quantum Dots Rate Reporting Research Personnel Resolution Role Severities Signal Pathway Signal Transduction Specific qualifier value Speed Syndrome System Testing Time Travel basal forebrain basal forebrain cholinergic neurons cellular imaging cholinergic fluorescence imaging mouse Ts65Dn nanometer neuronal cell body programs retrograde transport single molecule trafficking

项目摘要

DESCRIPTION (provided by applicant): Our broad objective is to understand the mechanisms by which the nerve growth factor (NGF) signal is propagated from the axon terminal to the cell body. NGF retrograde signaling is critical for the survival, differentiation, and maintenance of certain types neurons. Disrupted NGF retrograde transport was reported to contribute to the loss of the basal forebrain cholinergic (BFC) neurons in the brains of patients with Alzheimer's Disease or Down's Syndrome. This project will use advanced imaging techniques to directly visualize NGF transport in live neurons in real time. We focus on exploring dynamic features of NGF transport in normal and Down's Syndrome mice. The aims are: 1. Characterize the movement of NGF-containing endosomes in axons and define their pausing mechanism(s), by using quantum dot conjugated NGF to track endosomal movements with nanometer resolution. 2. Determine whether NGF-lacking endosomes are present, whether they are relevant for NGF signaling, and whether there are alternative signaling pathways independent of endosomal transport, by marking the NGF-lacking endosomes with photo-activatable green fluorescence proteins that are fused to the C-terminal of TrkA receptor. 3. Identify the abnormal features of disrupted NGF transport in Down Syndrome mouse neurons, by characterizing individual features of transport dynamics, which include the average speed, the moving speed, the pausing duration, and the pausing frequency. 4. Determine how amyloid precursor protein overexpression leads to the abnormal NGF retrograde transport in Down Syndrome mouse by examining how overexpression of amyloid precursor protein in DS mice might cause defective structural or axonal features that lead to disrupted NGF transport. Achieving those aims will increase our understanding of how NGF signal is propagated in normal and degenerative neurons. More broadly, those studies will contribute to elucidate the pathogenesis of Alzheimer's disease and Down syndrome.

描述（由申请人提供）：