Aging and susceptibility to hearing loss in zebrafish

描述（由申请人提供）：老化和噪声暴露如何相互作用产生听力损失是了解其病因的重要问题。年龄相关性听力损失（阿勒）和噪声性听力损失（NIHL）之间的关系并不总是相加的。使用哺乳动物模型的研究表明，在个体发育的极端时期，即在发育中的动物和衰老的动物中，对声损伤的敏感性可能最大。由于斑马鱼与人类基因间存在着相当程度的同线性，斑马鱼已成为研究胚胎发生和遗传缺陷的常用脊椎动物模型。因此，影响耳朵发育或与年龄相互作用以影响听力的斑马鱼突变可能揭示人类的类似病理。虽然在发育中的鱼类中已经研究了与年龄相关的听力变化，但在斑马鱼或任何其他硬骨鱼中还没有研究过衰老引起的退化的影响。为了充分了解内耳基因突变和NIHL在斑马鱼模型中的作用，需要野生型斑马鱼听力能力年龄相关变化的基线数据。拟议研究的目的是1）检查听力随年龄的变化，2）确定衰老（阿勒）和噪声暴露（NIHL）如何相互作用导致斑马鱼听力损失。为了实现这些目标，斑马鱼将在不同年龄段暴露于特定的声音暴露，然后检查内耳的病理学（通过扫描电子显微镜）和听力阈值（通过听觉脑干反应）。

DESCRIPTION (provided by applicant): How aging and noise exposure interact to produce hearing loss is an important issue for understanding its etiology. The relationship between age-related hearing loss (AHL) and noise-induced hearing loss (NIHL) is not always additive. Studies using mammalian models suggest that sensitivity to acoustic trauma may be greatest during the extremes of ontogeny - that is, in developing animals and in senescent animals. Zebrafish (Danio redo) have become a popular vertebrate model for examining embryogenesis and genetic defects because there is considerable synteny between zebrafish and human genes. Thus zebrafish mutations that affect ear development, or interact with age to affect hearing, may shed light on similar pathologies in humans. Although age-related shifts in hearing has been examined in developing fishes, the effects of degeneration due to senescence have not been examined in zebrafish or any other teleost. In order to fully understand the effects of inner ear genetic mutations and NIHL in the zebrafish model, baseline data of age-related shifts in hearing capabilities in wild type zebrafish are needed. The purposes of the proposed research will be to 1) examine shifts in hearing capabilities with age and 2) determine how aging (AHL) and noise exposure (NIHL) interact to cause hearing loss in zebrafish. To fulfill these goals, zebrafish will be exposed to specific sound exposures at various ages, and then pathology of the inner ear (via SEM) and hearing thresholds (via auditory brainstem response) will be examined.