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: 10475946
• 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: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10475946
• 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; 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要的公共卫生问题。阿格拉瓦尔等人。 (2009) 报告称 35% 的成年人 40岁以上有姿势不稳定的证据。平衡功能障碍与以下可能性增加有关 在美国，超过 50% 的意外死亡是由跌倒造成的。虽然造成的原因 前庭功能障碍是多种的，最近的研究表明噪音引起的听力损失和 前庭功能障碍（Akin 等人，2012 年；Golz 等人，2001 年；Guest 等人，2011 年；Zuniga 等人，2012 年）。建议 噪音暴露也是前庭功能障碍的一个危险因素这一说法存在争议，因为噪音暴露的影响有限。 噪声暴露与周围前庭病理学之间因果关系的实验支持 行为症状（例如平衡能力差）。在我们最近发表的研究中（Stewart et al. 2018），我们揭示了 将大鼠置于 120dB SPL 低频噪声（以 1500Hz 为中心的 3 个倍频程频带）下 6 小时，发现神经 通过前庭短潜伏期诱发电位评估，前庭神经活动减少 （VsEP）。暴露于噪音的动物也表现出花萼的免疫染色传入数量减少 末端，尤其是仅位于花萼的传入神经，终止于位于球囊纹状体区域的毛细胞 （斯图尔特等人，2018）。最近的实验表明，噪声，根据其强度，可能会导致 VsEP 对加加速度刺激的反应的暂时或永久阈值变化。永久噪声引起的 VsEP 阈值变化可以反映肾盏的损失和/或伴随的肾盏内带状突触的损失。这 损失可能是永久性的，也可能通过肾盏的重新连接或肾盏的恢复而恢复。 突触。我们假设噪音会破坏外周前庭突触和/或突触传递， 短暂或永久并导致功能性前庭丧失。 确定前庭周边突触/信号传递故障的基础和参数 确定破坏性噪音的特征是制定未来预防措施的关键第一步。 具体目标 1 将确定导致暂时或永久变化的噪声参数。 VsEP 和周围前庭神经末梢及其在囊状和椭圆囊中的突触 黄斑。具体目标 2 将扩展目标 1 的分析，以检查半规管嵴和 将噪音引起的嵴变化与耳石器官中观察到的变化进行比较。具体目标 3 将 将 VsEP 反应和噪声诱导的突触病理学变化与行为分析关联起来：光束 交叉任务、耳石依赖性行为（黄斑眼反射，MOR）和半规管依赖性 行为（前庭眼反射，VOR）。