Medial olivocochlear protection from environmental noise exposure

保护内侧橄榄耳蜗免受环境噪音暴露

• 批准号: 7545586
• 负责人: Amanda M. Lauer
• 金额: $ 4.96万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7545586
• 关键词: Acoustic Trauma; Acoustics; Acute; Adult; Afferent Neurons; Age; Aging; Anatomy; Animals; Auditory; Auditory Brainstem Responses; Auditory Physiology; Behavior; Behavioral; Biological; Biological Preservation; Cholinergic Receptors; Chronology; Communication impairment; Complex; Controlled Environment; Deterioration; Ear; Efferent Pathways; Electrons; End Point; Environment; Environmental Protection; Exhibits; Exposure to; Feedback; Genetically Engineered Mouse; Guidelines; Hair Cells; Hearing; Human; Immunofluorescence Immunologic; Impairment; Inbred Strain; Individual; Individual Differences; Injury; Investments; Laboratories; Laboratory Research; Laboratory mice; Labyrinth; Lead; Learning; Link; Long-Term Effects; Maintenance; Measures; Medial; Methods; Microscopic; Mus; Nature; Neurons; Noise; Noise-Induced Hearing Loss; Pattern; Performance; Personal Satisfaction; Persons; Phenotype; Physiological; Play; Populations at Risk; Predisposition; Presbycusis; Prevention; Prevention strategy; Procedures; Process; Range; Rate; Role; Scientist; Signal Transduction; Societies; Staging; Synapses; System; Testing; Time; Work; age related; aged; base; density; functional decline; genetic resource; hearing impairment; interest; mouse model; nerve supply; otoacoustic emission; protective effect; research study; response; sound; spiral ganglion; transmission process

DESCRIPTION (provided by applicant): Humans exhibit a wide range of vulnerability to sound exposure. These individual differences make it difficult to develop accurate guidelines for hearing conservation that are effective and realistic for an industrialized society. The strength of natural olivocochlear (OC) efferent feedback mechanisms may be a primary determinant of individual susceptibility to noise-induced hearing loss accumulated over a lifetime. To test this hypothesis, Aim 1 will relate patterns of hearing loss to the OC function of laboratory mice. The strength of OC function will be manipulated by selecting subjects from normal strains based on physiological criteria, investigating inbred strains with compromised OC systems, and disrupting OC signaling in genetically engineered mice. There is strong evidence that OC neurons protect the ear from sound exposure. The ecological significance of the protective effect has been questioned because it has been demonstrated only at extreme sound levels. OC neurons may also protect the ear from the accrued effects of long-term moderate sound exposure. Aging subjects in quiet versus moderate sound levels will test this hypothesis. Cochlear integrity will be evaluated with distortion product otoacoustic emissions and auditory brainstem responses. The chronology of hearing loss will be characterized longitudinally within groups of mice that are defined by age, OC strength, and cumulative sound exposure. Based on human communication impairments, elevated physiological thresholds are expected to represent the endpoint of a functional decline that begins earlier as deficits in listening in noise. Aim 2 will confirm this prediction by tracking the perceptual changes in each group with a signal-in-noise behavioral task. The objective is to demonstrate behavioral deficits in background noise before the onset of physiological threshold shifts. The anatomical correlates of these diverse forms of hearing loss have been difficult to isolate because experimental animals, like humans, show large individual differences in the rate and pattern of impairment. The physiological and behavioral phenotypes achieved in the experiments of Aims 1 and 2 provide an ideal context for investigating the anatomical basis of hearing loss and concurrent compensatory mechanisms in the inner ear. Aim 3 will use quantitative immunofluorescence and electron microscopic analyses to describe the afferent and efferent synaptic complexes of mice with known processing deficits. Long-term maintenance of auditory function is predicted to require the survival of afferent neurons and functional efferent innervation. Relevance: Results from this work will lead to a better understanding of the protective effects of the OC system, and may lead to better hearing loss prevention strategies in humans.

描述（由申请人提供）：人类表现出广泛的声音曝光脆弱性。这些个体差异使得很难制定准确的听力保护准则，这些准则对工业化社会是有效且现实的。天然橄榄石（OC）传出反馈机制的强度可能是个人对噪声引起的听力损失的敏感性的主要决定因素。为了检验这一假设，AIM 1将将听力损失模式与实验室小鼠的OC功能相关联。 OC功能的强度将通过根据生理标准从正常菌株中的受试者进行操纵，研究受损OC系统的近交菌株，并破坏基因工程小鼠的OC信号传导。有强有力的证据表明OC神经元可以保护耳朵免受声音暴露。保护效应的生态意义受到质疑，因为它仅在极端的声音水平上得到证明。 OC神经元还可以保护耳朵免受长期中度声音暴露的应计影响。在安静与中等声音水平中的老化受试者将检验这一假设。人工耳蜗完整性将通过失真产物耳声排放和听觉脑干反应进行评估。听力损失的年表将在小鼠组中纵向表征，这些小鼠由年龄，OC强度和累积声音暴露定义。基于人类的交流障碍，预计生理阈值升高代表了功能下降的终点，该功能下降开始于较早的噪声倾听。 AIM 2将通过通过信号噪声行为任务跟踪每个组的感知变化来确认这一预测。目的是在生理阈值转移开始之前证明背景噪声中的行为缺陷。这些不同形式的听力损失形式的解剖学相关性很难分离，因为像人类这样的实验动物在损害的速率和模式上表现出很大的个体差异。目标1和2实验中实现的生理和行为表型为研究内耳中听力损失和同时补偿机制的解剖基础提供了理想的背景。 AIM 3将使用定量免疫荧光和电子显微镜分析来描述患有已知加工缺陷的小鼠的传入和传出突触复合物。预计听觉功能的长期维护需要传入神经元和功能传递神经的存活。相关性：这项工作的结果将使人们对OC系统的保护作用有更好的了解，并可能导致人类更好的预防听力损失策略。