Noise-Induced Synaptic Loss and Vestibular Dysfunction

噪音引起的突触丧失和前庭功能障碍

基本信息

批准号：
9933644
负责人：
WILLIAM M KING
金额：
$ 15.6万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9933644
关键词：
Action Potentials Adult Affect Age Air American Animals Attenuated Audiology Auditory Behavior Behavioral Behavioral Assay 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 Measures Musculoskeletal Equilibrium Neurons Noise Noise-Induced Hearing Loss Occupational 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 Vestibular Nerve Vestibular loss attenuation 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

项目摘要

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, especially for a causal relationship between noise exposure and vestibular pathology. In our recently 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 attenuation of VsEP responses to jerk stimuli. Noise induced increases in VsEP jerk thresholds could reflect loss of some calyces and/or concomitant loss of ribbon synapses within reconnected calyces. This loss could be permanent or there could be recovery associated with reconnection of calyces. 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 sacculus. 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 sacculus. 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。实验支持，特别是噪声暴露与前庭病理之间的因果关系。在我们最近的研究 (Stewart et al. 2018)，我们将大鼠暴露于 120dB SPL 低频噪声 (3- 倍频带以 1500Hz 为中心），发现前庭神经的神经活动减少，如通过前庭短潜伏期诱发电位（VsEP）进行评估。暴露于噪音的动物也表现出具有花萼末端的免疫染色传入神经数量减少，尤其是终止的仅花萼传入神经位于球囊纹状体区域的毛细胞（Stewart et al. 2018）。最近的实验表明噪声可能会导致 VsEP 响应暂时或永久衰减，具体取决于其强度猛烈刺激。噪声引起的 VsEP 冲击阈值增加可能反映了一些肾盏的损失和/或重新连接的肾盏内的带状突触随之丧失。这种损失可能是永久性的，也可能是与肾盏重新连接相关的恢复。我们假设噪音会扰乱外周前庭突触和/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 以及周围前庭神经末梢及其在球囊中的突触。具体目标 2 将扩展目标 1 的分析以检查半规管嵴并比较噪声引起的变化嵴与在球囊中观察到的嵴。具体目标 3 将 VsEP 反应的变化与噪声诱导的突触病理学与行为分析：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）。