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: 10584770
• 负责人: WILLIAM M KING
• 金额: $ 20.44万
• 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: 2020-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10584770
• 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

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).

摘要 前庭功能障碍是一个重要的公共卫生问题。Agrawal等人（2009年）报告说，35%的成年人 40岁以上的人有姿势不稳定的迹象。平衡功能障碍与以下可能性增加有关： 在美国，超过50%的意外死亡是由福尔斯跌倒造成的。虽然原因 前庭功能障碍是多种多样的，最近的研究表明，噪音引起的听力损失和 前庭功能障碍（Akin et al. 2012; Golz et al. 2001; Guest et al. 2011; Zuniga et al 2012）。的建议 噪声暴露也是前庭功能障碍的危险因素是有争议的，因为只有有限的 实验支持噪声暴露和外周前庭病理之间的因果关系， 行为症状（例如，平衡差）。在我们最近发表的研究（Stewart et al. 2018）中，我们暴露了 大鼠暴露于120 dBSPL低频噪声（中心频率为1500 Hz的3倍频程噪声）6小时，发现神经元 前庭短潜伏期诱发电位检测显示，前庭神经活动减少 （VsEP）。噪声暴露的动物也表现出减少的免疫染色传入与花萼 终末，特别是终止于位于小囊纹状区的毛细胞的仅花萼传入 （Stewart et al. 2018）。最近的实验表明，噪音，根据其强度，可以导致 VsEP对jerk刺激反应的暂时或永久性阈值偏移。永久性噪声诱发VsEP 阈值偏移可以反映肾盏的丧失和/或伴随的肾盏内带状突触的丧失。这 丢失可能是永久性的，也可能是与肾盏重新连接相关的恢复， 突触我们假设噪音破坏了前庭神经突触和/或突触传递， 暂时性或永久性的，并导致功能性前庭丧失。 确定前庭周围神经突触/信号传递失败的基础和参数 对破坏性噪声进行表征是发展未来预防措施的关键的第一步。 具体目标1将确定噪声参数，导致暂时与永久的变化， VsEP和前庭周围神经终末及其在囊状和椭圆囊内的突触 斑。具体目标2将扩展目标1的分析，以检查半规管嵴， 比较噪声引起的嵴变化与耳石器官中观察到的变化。第3章将 将VsEP反应的变化和噪声诱导的突触病理与行为测定相关联： 交叉任务，耳石依赖性行为（黄斑眼反射，莫尔），半规管依赖性 行为（前庭眼反射，VOR）。