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

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

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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，跌倒造成了超过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，特别是对于噪声暴露与前庭病理学之间的因果关系。在我们最近的研究（Stewart等人，2018年），我们将大鼠暴露于120dB SPL低频噪声的6小时（3-- 八度带以1500Hz为中心），发现前庭神经中的神经活动减少，因为由前庭短潜伏期（VSEP）评估。噪音暴露的动物也表现出来减少了具有花萼末端的免疫染色传入数量，尤其是仅花萼的传入量在位于囊的Striolar区域的毛细胞上（Stewart等，2018）。最近的实验显示该噪声取决于其强度，可能会导致VSEP响应的暂时或永久衰减刺激刺激。噪声引起的VSEP混蛋阈值增加可能反映了某些钙的损失和/或在重新连接的钙中伴随着色带突触的丧失。这种损失可能是永久的，也可以与重新连接有关的恢复。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在囊中的突触。具体目标2将扩展AIM 1的分析以检查半圆形管骨并比较噪声引起的变化在囊中观察到的cristae。特定的目标3将与VSEP响应的变化相关联和噪声引起的突触病理和行为测定：梁交叉任务，耳石依赖性行为（黄斑眼反射，MOR）和半圆形管依赖的行为（前庭反射，vor）。