Proteomic analyses 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是很重要的。探索这些变化的一个卓有成效的模型系统是小鸡的脑干听觉系统。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。观察到这些神经元内特定蛋白质的快速变化（几小时内）。本研究旨在进一步确定耳聋后早期耳蜗核神经元蛋白的变化。这将有助于更好地理解这些神经元的竞争死亡和生存机制，并可能有助于开发有针对性的干预措施来促进神经元的存活。此外，对耳聋的长期调整将在这种侮辱中幸存下来的细胞中进行评估。最后，该研究将研究与耳蜗核神经元核糖体特异性相互作用的蛋白质，这些蛋白质可能有助于这些细胞的最终死亡。

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.