Drosophila model for noise-induced hearing loss

描述（由申请人提供）：尽管噪音引起的听力损失对人类的职业和娱乐健康很重要，但我们对这个问题的了解相当初级。这种损伤是永久性的，因为哺乳动物一旦死亡，它们的听觉毛细胞就无法再生。对噪音引起的听力损失的潜在原因的研究主要集中在细胞的机械损伤上，而分子研究则集中在氧化损伤和细胞骨架破坏上。哺乳动物研究面临着进入颞骨内耳的困难和昂贵的动物护理费用的挑战。在这个建议中，我们试图利用遗传模式生物，果蝇，系统地表征由急性或慢性过度暴露于声音引起的基因表达变化。我们的初步结果表明，急性暴露对听觉功能有很强的直接影响。我们建议首先研究这些形式的噪音创伤的即时和长期形态学和生理后果。其次，我们将使用微阵列分析识别全基因组对声应力的反应。这些研究将提供可能的途径，通过这些途径来增加对噪音损害的抵抗力，作为一种预防措施，或者在事实发生后减少噪音损害的有害影响，作为一种治疗措施。他们还将告知个体对噪音损伤易感性的遗传差异。

DESCRIPTION (provided by applicant): Our understanding of Noise-Induced Hearing Loss is rather rudimentary, despite the importance of this problem to human occupational and recreational health. The damage is permanent because mammals cannot regenerate their auditory hair cells once they die. Studies of the underlying causes of noise-induced hearing loss have focused on mechanical damage to cells, and molecular studies centered around oxidative damage and cytoskeletal disruptions. Mammalian studies are challenged by difficult access to the inner ear inside the temporal bone, and expensive animal care costs. In this proposal we seek to capitalize on the genetic model organism, Drosophila, to systematically characterize gene expression changes induced by acute or chronic over-exposure to sound. Our preliminary results show that there are strong immediate effects on auditory function after acute exposure. We propose first to study the immediate and longer-term morphological and physiological consequences of these forms of noise trauma. Second, we will identify genome-wide responses to acoustic stress using microarray analysis. These studies will provide insight into possible pathways through which to increase resistance to noise damage as a preventative measure, or to reduce the deleterious effects of noise damage after the fact as a therapeutic measure. They will also inform the individual genetic differences in susceptibility to noise damage. PUBLIC HEALTH RELEVANCE: Over-exposure to noise is a serious problem in today's industrial and technological world, especially with increasing age structure in human populations. The proposed project uses the genetic model organism Drosophila to investigate functional and structural consequences to the auditory organ upon acute or chronic over-exposure to sound, and to understand gene expression changes evoked by this treatment. The results of our studies will facilitate identification of putative preventative and therapeutic targets for human noise-induced hearing loss and age-related hearing loss.