Proteomic analyses following deafness

耳聋后的蛋白质组学分析

• 批准号: 7977482
• 负责人: RICHARD L. HYSON
• 金额: $ 16.84万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7977482
• 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; Face; 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

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耳聋后中枢神经系统的变化。由于人工耳蜗植入等干预措施对长期耳聋的神经系统起作用，因此了解这些存活细胞组成的可能变化以优化此类干预措施非常重要。一个富有成效的模型系统，探索这些变化一直是脑干听觉系统的小鸡。耳聋导致鸟类耳蜗核神经元的快速变化，并最终导致20-30%的这些神经元死亡。在这些神经元内的特定蛋白质中观察到快速变化（在数小时内）。这项拟议中的研究旨在进一步确定耳聋后早期耳蜗核神经元中的蛋白质变化。这将导致对这些神经元中参与的竞争性死亡和存活机制的更深入理解，并可能有助于开发有针对性的干预措施以促进神经元的存活。此外，对耳聋的长期调整将在这种损伤存活的细胞中进行评估。最后，拟议的研究将调查与耳蜗核神经元的核糖体特异性相互作用的蛋白质，这可能有助于这些细胞的最终死亡。 公共卫生相关性：耳聋导致中枢神经系统神经元死亡。这个过程涉及蛋白质的变化，这些蛋白质有助于竞争死亡和生存途径。该项目将鉴定参与这些途径的蛋白质，特别是可能参与核糖体功能障碍的蛋白质。这可能会导致有针对性的干预措施，可以促进神经元在许多条件下的存活，如神经退行性疾病，以及耳聋。