Proteomic analyses following deafness

耳聋后的蛋白质组学分析

基本信息

批准号：
8076227
负责人：
RICHARD L. HYSON
金额：
$ 17.3万
依托单位：
FLORIDA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-01 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8076227
关键词：
Accounting Amino Acids Auditory Auditory system Biological Assay Biological Models Birds Brain Brain Stem Cell Death Cell Nucleus Cell Survival Cells Cellular biology Cessation of life Cochlea Cochlear Implants Cochlear nucleus Deafferentation procedure Development Epitopes Excision Fluorescence Functional disorder Future Goals Hour Immunohistochemistry In Situ Hybridization Intervention Label Lead Life Masks Mass Spectrum Analysis Messenger RNA Monoclonal Antibodies Nervous system structure Neuraxis Neurodegenerative Disorders Neurons Neurosciences Pathway interactions Pattern Phosphorylation Play Population Process Protein Biosynthesis Proteins Proteomics Recovery of Function Regulation Research Ribosomes Role Sensory Sensory Deprivation Techniques Testing Time Two-Dimensional Gel Electrophoresis Work deafness experience nerve supply neuron loss neuronal survival novel partial recovery public health relevance research study sensory system two-dimensional

项目摘要

DESCRIPTION (provided by applicant): One important goal of contemporary auditory neuroscience is to understand the changes in the central nervous system that follow deafness. Since interventions, such as cochlear implants, work on a nervous system that has had long-lasting deafness, it is important to understand the possible changes in the makeup of these surviving cells so as to optimize such interventions. A fruitful model system for exploring these changes has been the brain stem auditory system of the chick. Deafness results in rapid changes in avian cochlear nucleus neurons and the eventual death of 20-30% of these neurons. Rapid changes (within hours) are observed in specific proteins within these neurons. The proposed research seeks to further define the protein changes in cochlear nucleus neurons in the early hours following deafness. This will lead to a greater understanding of the competing death and survival mechanisms engaged in these neurons and may help develop targeted interventions to promote the survival of neurons. In addition, long-term adjustments to deafness will be evaluated in cells that survive this insult. Finally, the proposed research will investigate proteins that specifically interact with the ribosomes of deafened cochlear nucleus neurons that may contribute to the ultimate demise of these cells. PUBLIC HEALTH RELEVANCE: Deafness results in the death of neurons in the central nervous system. This process involves changes in proteins that contribute to competing death and survival pathways. This project will identify proteins involved in these pathways and specifically proteins that may be involved in ribosomal dysfunction. This may lead to targeted interventions that could promote neuronal survival in a number of conditions, such as neurodegenerative disease, as well as following deafness.

描述（由申请人提供）：当代听觉神经科学的一个重要目标是了解中枢神经系统的变化遵循耳聋。自从干预措施（例如人工耳蜗）上，在具有长期聋哑的神经系统上工作，重要的是要了解这些存活细胞的构成可能的变化很重要，以优化此类干预措施。探索这些变化的富有成果的模型系统是小鸡的脑干听觉系统。耳聋导致鸟耳蜗神经元的快速变化，这些神经元中有20-30％死亡。在这些神经元内的特定蛋白质中观察到快速变化（数小时之内）。拟议的研究旨在进一步定义耳聋后凌晨的耳蜗神经元的蛋白质变化。这将导致对参与这些神经元的竞争死亡和生存机制有更深入的了解，并可能有助于制定有针对性的干预措施以促进神经元的生存。此外，将在生存这种侮辱的细胞中评估对耳聋的长期调整。最后，拟议的研究将研究与聋哑的耳蜗神经元的核糖体特别相互作用的蛋白质，这可能导致这些细胞的最终灭绝。公共卫生相关性：耳聋导致中枢神经系统中神经元死亡。该过程涉及有助于竞争死亡和生存途径的蛋白质的变化。该项目将鉴定涉及核糖体功能障碍可能涉及的蛋白质涉及的蛋白质。这可能导致有针对性的干预措施，这些干预措施可能会在许多疾病（例如神经退行性疾病）以及聋哑人中促进神经元存活。