Consequences of chronic noise exposure in nonhuman primates

非人类灵长类动物长期暴露于噪音的后果

• 批准号: 10608454
• 负责人: Brandon C. Cox
• 金额: $ 73.06万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2028-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10608454
• 关键词: Adopted; Adult; Affect; Anatomy; Animal Model; Animals; Audiology; Auditory; Auditory Brainstem Responses; Behavioral; Behavioral Assay; Binaural; Biological Markers; Cell Death; Cell physiology; Characteristics; Chronic; Clinical; Cochlea; Complex; Data; Development; Disease; Dose; Early Diagnosis; Electrophysiology (science); Environment; Euthanasia; Exposure to; Female; Frequencies; Hair Cells; Hearing; Hearing Tests; Histology; Histopathology; Hour; Human; Individual; Injury; Inner Hair Cells; Laboratories; Loudness; Macaca; Masks; Measurable; Measures; Modeling; Monitor; Monkeys; Natural regeneration; Noise; Noise-Induced Hearing Loss; Occupational; Occupational Exposure; Occupational Noise; Occupational injury; Outcome; Outer Hair Cells; Pathology; Pattern; Performance; Phenotype; Phylogenetic Analysis; Physiological; Predisposition; Prevention program; Primates; Protocols documentation; Psychophysics; Recovery; Recreation; Reflex action; Reporting; Research Design; Rodent; Rodent Model; Study models; Synapses; Temporary Threshold Shift; Testing; Time; Training; Work; auditory processing; clinically significant; design; detection assay; dosage; ear muscle; experience; hearing impairment; histological studies; in vivo; insight; male; middle ear; mouse model; noise exposure; nonhuman primate; normal hearing; otoacoustic emission; prevent hearing loss; response; ribbon synapse; signal processing; sound; timeline

ABSTRACT Noise-induced hearing loss (NIHL, including clinically measurable audiometric threshold shifts) affects over 25 million adults, with the primary cause being exposure to occupational or other loud environmental sound. However, many noise-exposed individuals report difficulty hearing in noisy environments without clinically significant threshold increases. Animal model studies have revealed potential mechanisms of noise induced hearing difficulties (NIHD) and their accompanying psychophysical and physiological changes, including a candidate mechanism (with evidence from rodent models and emerging support from the macaque model) for clinically normal hearing with difficulty in noisy environments: cochlear synapse loss. However, animal models typically use single exposure protocols to create cochlear pathology, which are unlike the chronic noise exposures leading to NIHL in humans, who experience smaller, repeated daily noise doses that result in NIHL. Data from our macaque model of NIHL (having noise susceptibility similar to humans) suggests that the single exposure noise levels needed to induce NIHL and cochlear synapse loss are much higher than sound levels typically experienced by humans occupationally or recreationally. Nonetheless, preliminary data in macaques show that single noise exposures that cause temporary threshold shifts (TTS) result in cochlear synapse loss 2- months post exposure but not at 10-months post-exposure, and auditory processing deficits. This project will expand these early observations to more realistic chronic noise exposures similar to those experienced by workers. We propose psychophysical, physiological, and histological studies 1) to establish a timeline for the development of sustained auditory processing deficits and cochlear pathology in macaques chronically exposed to noise, and 2) to define behavioral and electrophysiological assays that detect changes in hearing that develop prior to permanent threshold shifts (PTS). Our hypothesis is that chronic noise exposures (8 hours a day, 5 days a week) cause a sequence of non-transient NIHD that progress to PTS. Specifically, we predict that chronic noise exposures will cause psychophysical changes (Aim 1): the earliest deficits will be in spatial and temporal processing, followed by deficits in processing signals in noise, followed by audiometric deficits (PTS). Physiological changes (Aim 2) will parallel psychophysical changes: earliest deficits will be in middle ear muscle reflex (MEMR) and measures of binaural and temporal processing, followed by deficits in distortion product otoacoustic emission (DPOAE) amplitudes and masked auditory brainstem responses (ABR), followed by deficits in DPOAEs and ABR thresholds. These deficits will be paralleled by cochlear pathology: early, non-transient cochlear synapse loss, followed by outer hair cell loss, followed by a combination of outer and inner hair cell loss (Aim 3). The results of these studies will reveal sensitive markers of early auditory damage with realistic noise exposures, and the sequence of cochlear pathology. Study results will be used to develop reliable, clinically viable early indicators of NIHL and enhance hearing loss prevention program outcomes.

抽象的 噪音引起的听力损失（NIHL，包括临床可测量的听力阈值偏移）影响超过 25 数百万成年人，主要原因是接触职业或其他大声的环境声音。 然而，许多暴露于噪音的人报告在噪音环境中听力困难而没有进行临床治疗。 阈值显着增加。动物模型研究揭示了噪声诱导的潜在机制 听力困难（NIHD）及其伴随的心理物理和生理变化，包括 候选机制（来自啮齿动物模型的证据和来自猕猴模型的新支持） 临床上听力正常，但在嘈杂的环境中却有困难：耳蜗突触丧失。然而，动物模型 通常使用单次暴露协议来创建耳蜗病理学，这与慢性噪声不同 人类暴露于导致 NIHL 的噪声中，每天重复接触较小的噪声剂量会导致 NIHL。 来自我们的 NIHL 猕猴模型（具有与人类相似的噪音敏感性）的数据表明，单一 诱发 NIHL 和耳蜗突触损失所需的暴露噪音水平远高于声音水平 通常由人类在职业或娱乐中经历。尽管如此，猕猴的初步数据 表明导致暂时阈值偏移 (TTS) 的单一噪声暴露会导致耳蜗突触损失 2- 暴露后几个月但不是暴露后 10 个月，以及听觉处理缺陷。该项目将 将这些早期观察结果扩展到更现实的慢性噪声暴露，类似于 工人。我们建议进行心理物理学、生理学和组织学研究 1) 建立一个时间表 长期接触的猕猴出现持续的听觉处理缺陷和耳蜗病理 噪音，以及 2) 定义行为和电生理学检测，检测听力发生的变化 在永久阈值偏移（PTS）之前。我们的假设是，长期暴露于噪音（每天 8 小时，5 天） 一周）导致一系列非暂时性 NIHD 进展为 PTS。具体来说，我们预测慢性 噪音暴露会导致心理物理变化（目标 1）：最早的缺陷将出现在空间和时间上 处理方面的缺陷，其次是噪声中处理信号的缺陷，然后是听力测定缺陷（PTS）。 生理变化（目标 2）将与心理物理变化并行：最早的缺陷将出现在中耳肌肉 反射（MEMR）以及双耳和时间处理的测量，其次是失真产物的缺陷 耳声发射 (DPOAE) 振幅和掩蔽听觉脑干反应 (ABR)，然后是缺陷 DPOAE 和 ABR 阈值。这些缺陷将与耳蜗病理学并行：早期、非暂时性 耳蜗突触损失，然后是外毛细胞损失，然后是外毛细胞和内毛细胞损失的组合 （目标 3）。这些研究的结果将揭示早期听觉损伤与真实噪音的敏感标记 暴露以及耳蜗病理学的顺序。研究结果将用于开发可靠的、临床的 NIHL 的可行早期指标并增强听力损失预防计划的成果。