Noise-Induced Synaptic Loss and Vestibular Dysfunction

噪音引起的突触丧失和前庭功能障碍

• 批准号: 10513362
• 负责人: WILLIAM M KING
• 金额: $ 1.4万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-10 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10513362
• 关键词: Action Potentials; Adult; Affect; Age; Air; American; Animals; Attenuated; Audiology; Auditory; Behavior; Behavioral; Behavioral Assay; Behavioral Symptoms; Cavia; Cessation of life; Characteristics; Clinical; Crista ampullaris; Data; Development; Disease; Elderly; Equilibrium; Evoked Potentials; Exhibits; Exposure to; Eye; Eye Movements; Failure; Frequencies; Functional disorder; Future; Grant; Hair Cells; Head; Hour; Intervention; Label; Labyrinth; Lesion; Link; Loudness; Musculoskeletal Equilibrium; Neurons; Noise; Noise-Induced Hearing Loss; Occupational; Organ; Pathology; Patients; Peripheral; Pharmaceutical Preparations; Positioning Attribute; Posture; Preventive measure; Public Health; Publishing; Rattus; Recovery; Reflex action; Reporting; Risk Factors; Semicircular canal structure; Signal Transduction; Stains; Stimulus; Suggestion; Synapses; Synaptic Transmission; System; Temporary Threshold Shift; Testing; Time; Training; Type I Hair Cell; Utricle structure; Utricular macula; Vestibular Nerve; Vestibular loss; equilibration disorder; excitotoxicity; experimental study; falls; hearing impairment; hidden hearing loss; macula; noise exposure; otoconia; posture instability; relating to nervous system; response; ribbon synapse; sound; synaptic function; transmission process; vestibulo-ocular reflex; Action Potentials; Adult; Affect; Age; Air; American; Animals; Attenuated; Audiology; Auditory; Behavior; Behavioral; Behavioral Assay; Behavioral Symptoms; Cavia; Cessation of life; Characteristics; Clinical; Crista ampullaris; Data; Development; Disease; Elderly; Equilibrium; Evoked Potentials; Exhibits; Exposure to; Eye; Eye Movements; Failure; Frequencies; Functional disorder; Future; Grant; Hair Cells; Head; Hour; Intervention; Label; Labyrinth; Lesion; Link; Loudness; Musculoskeletal Equilibrium; Neurons; Noise; Noise-Induced Hearing Loss; Occupational; Organ; Pathology; Patients; Peripheral; Pharmaceutical Preparations; Positioning Attribute; Posture; Preventive measure; Public Health; Publishing; Rattus; Recovery; Reflex action; Reporting; Risk Factors; Semicircular canal structure; Signal Transduction; Stains; Stimulus; Suggestion; Synapses; Synaptic Transmission; System; Temporary Threshold Shift; Testing; Time; Training; Type I Hair Cell; Utricle structure; Utricular macula; Vestibular Nerve; Vestibular loss; equilibration disorder; excitotoxicity; experimental study; falls; hearing impairment; hidden hearing loss; macula; noise exposure; otoconia; posture instability; relating to nervous system; response; ribbon synapse; sound; synaptic function; transmission process; vestibulo-ocular reflex

Abstract Vestibular dysfunction is a significant public health problem. Agrawal et al. (2009) reported that 35% of adults older than 40 had evidence of postural instability. Balance dysfunction is linked to an increased likelihood of falling and in the U.S. falls are responsible for more than 50% of accidental deaths. Although the causes of vestibular dysfunction are multiple, recent studies suggest a linkage between noise-induced hearing loss and vestibular dysfunction (Akin et al. 2012; Golz et al. 2001; Guest et al. 2011; Zuniga et al 2012). The suggestion that noise exposure is also a risk factor for vestibular dysfunction is controversial as there is only limited experimental support for causal relationships between noise exposure and peripheral vestibular pathology and behavioral symptoms (e.g., poor balance). In our recently published study (Stewart et al. 2018), we exposed rats to 6 hours of 120dB SPL low frequency noise (3-octave band centered at 1500Hz) and found that neural activity in the vestibular nerve was reduced, as assessed by the vestibular short latency evoked potential (VsEP). Noise exposed animals also exhibited reduced numbers of immunostained afferents with calyx endings, especially calyx-only afferents that terminate on hair cells located in the striolar region of the sacculus (Stewart et al. 2018). More recent experiments show that noise, depending on its intensity, can cause either temporary or permanent threshold shifts of VsEP responses to jerk stimuli. Permanent noise induced VsEP threshold shifts could reflect loss of calyces and/or concomitant loss of ribbon synapses within calyces. This loss might be permanent or there could be recovery associated with reconnection of calyces or recovery of synapses. We hypothesize that noise disrupts peripheral vestibular synapses and/or synaptic transmission, transiently or permanently and causes functional vestibular loss. Determining the basis for synaptic/signal transmission failure in the vestibular periphery and the parameters that characterize damaging noise is a critical first step toward development of future preventative measures. Specific Aim 1 will determine the parameters of noise that causes temporary versus permanent changes to the VsEP and to peripheral vestibular nerve terminals and their synapses in the saccular and utricular maculae. Specific Aim 2 will extend the analysis of Aim 1 to examine the semicircular canal cristae and compare noise-induced changes in the cristae with those observed in the otolith organs. Specific Aim 3 will correlate changes in VsEP responses and noise induced synaptic pathology with behavioral assays: a beam crossing task, an otolith dependent behavior (macular ocular reflex, MOR), and a semicircular canal dependent behavior (vestibuloocular reflex, VOR).

抽象的 前庭功能障碍是一个重大的公共卫生问题。 Agrawal等。 （2009年）报道了35％的成年人 40岁以上有姿势不稳定的证据。平衡功能障碍与增加的可能性有关 跌倒，在美国瀑布造成了超过50％的意外死亡。虽然原因是 前庭功能障碍是多个，最近的研究表明，噪声引起的听力损失与 前庭功能障碍（Akin等，2012; Golz等，2001; Guest etal。2011; Zuniga et al 2012）。建议 噪声暴露也是前庭功能障碍的危险因素，因为只有有限 实验支持噪声暴露与周围前庭病理学之间的因果关系和 行为症状（例如，平衡差）。在我们最近发表的研究（Stewart等，2018）中，我们暴露了 大鼠至6小时的120dB SPL低频噪声（以1500Hz为中心），发现神经 前庭短篇潜伏期诱发的潜力减少了前庭神经的活性 （VSE）。噪声暴露的动物还表现出减少了卡雅的免疫染色传入量 结尾，尤其是终止位于Sacculus Striolar区域的毛细胞上的仅花萼的传入 （Stewart等人，2018年）。最近的实验表明，噪声取决于其强度，可能会导致 VSEP对混蛋刺激的暂时或永久阈值转移。永久噪声引起的VSEP 阈值移位可能反映了钙符号的损失和/或卷曲内丝带突触的丧失。这 损失可能是永久的，或者可能与重新连接或恢复相关的恢复 突触。我们假设噪声破坏了外围前庭突触和/或突触传播， 瞬时或永久性，并导致功能性前庭损失。 确定前庭外围和参数中突触/信号传递失败的基础 这种特征的破坏性噪声是朝着未来预防措施发展的关键第一步。 具体目标1将确定导致暂时性与永久变化的噪声参数 VSEP和外围前庭神经末端及其突触 黄斑。特定的目标2将扩展对目标1的分析，以检查半圆形的cristae和 比较噪声引起的Cristae的变化与耳石器官中观察到的变化。具体的目标3将 将VSEP响应的变化和噪声引起的突触病理与行为分析相关联：光束 跨任务，耳石依赖性行为（黄斑眼反射，MOR）和半圆形管依赖 行为（前庭反射，vor）。