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:
- 金额:$ 15.6万
- 依托单位:
- 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:
- 关键词:Action PotentialsAdultAffectAgeAirAmericanAnimalsAttenuatedAudiologyAuditoryBehaviorBehavioralBehavioral AssayCaviaCessation of lifeCharacteristicsClinicalCrista ampullarisDataDevelopmentDiseaseElderlyEquilibriumEvoked PotentialsExhibitsExposure toEyeEye MovementsFailureFrequenciesFunctional disorderFutureGrantHair CellsHeadHourInterventionLabelLabyrinthLesionLinkLoudnessMeasuresMusculoskeletal EquilibriumNeuronsNoiseNoise-Induced Hearing LossOccupationalPathologyPatientsPeripheralPharmaceutical PreparationsPositioning AttributePosturePreventive measurePublic HealthPublishingRattusRecoveryReflex actionReportingRisk FactorsSemicircular canal structureSignal TransductionStainsStimulusSuggestionSynapsesSynaptic TransmissionSystemTemporary Threshold ShiftTestingTimeTrainingType I Hair CellUtricle structureVestibular NerveVestibular lossattenuationequilibration disorderexcitotoxicityexperimental studyfallshearing impairmenthidden hearing lossmaculaotoconiaposture instabilityrelating to nervous systemresponseribbon synapsesoundsynaptic functiontransmission processvestibulo-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).
摘要
前庭功能障碍是一个重要的公共卫生问题。Agrawal等人。(2009)报告称,35%的成年人
40岁以上的患者有姿势不稳定的证据。平衡功能障碍与罹患
坠落和在美国,坠落造成的意外死亡人数超过50%。尽管造成这种情况的原因
前庭功能障碍是多方面的,最近的研究表明噪音导致的听力损失和
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)。这个建议
噪声暴露也是前庭功能障碍的一个危险因素是有争议的,因为只有有限的
实验支持,尤其是噪声暴露和前庭病理之间的因果关系。在……里面
我们最近的研究(Stewart等人)2018年),我们将大鼠暴露在120dBSPL低频噪声(3-
倍频程集中在1500赫兹),发现前庭神经的神经活动减少,因为
用前庭短潜伏期诱发电位(VsEP)进行评估。暴露在噪音中的动物也展出了
带有花萼末端的免疫染色传入神经的数量减少,特别是终止的仅有花萼的传入神经
位于球囊纹状体区域的毛细胞(Stewart等人)。2018年)。最近的实验表明
根据其强度不同,该噪声可导致VsEP反应的暂时性或永久性衰减
来刺激刺激。噪声引起的VsEP急动阈值的增加可能反映了一些花瓣和/或
随之而来的是重新连接的肾盏内带状突触的丢失。这种损失可能是永久性的,也可能是
与肾盏重联相关的恢复。我们假设噪音干扰了外周前庭
突触和/或突触传递,暂时性或永久性,并导致功能性前庭丧失。
确定前庭周围突触/信号传递失败的基础和参数
这一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将确定导致临时与永久性变化的噪声参数
VsEP和球囊内的前庭外周神经末梢及其突触。特定目标2将
扩展Aim 1的分析以检查半规管嵴并比较噪声引起的改变
与球囊内观察到的眉骨一致。特定目标3将VsEP反应的变化与
噪声诱发突触病理的行为分析:横梁交叉任务,耳石依赖行为
(黄斑眼反射,MOR)和半规管依赖行为(前庭眼反射,VOR)。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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WILLIAM M KING其他文献
WILLIAM M KING的其他文献
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{{ truncateString('WILLIAM M KING', 18)}}的其他基金
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 - 财政年份:2021
- 资助金额:
$ 15.6万 - 项目类别:
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 - 财政年份:2020
- 资助金额:
$ 15.6万 - 项目类别:
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:
10372065 - 财政年份:2020
- 资助金额:
$ 15.6万 - 项目类别:
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 - 财政年份:2020
- 资助金额:
$ 15.6万 - 项目类别:
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:
10612731 - 财政年份:2020
- 资助金额:
$ 15.6万 - 项目类别:
Sound Evoked Eye and Head Movements Mediated by Vestibulo-Collic and Vestibulo-Ocular Reflex (VOR, VCR) Pathways: a Physiological Basis for Noise Induced Vestibular Loss (NIVL)
前庭-结肠和前庭-眼反射 (VOR、VCR) 通路介导的声音诱发的眼睛和头部运动:噪声引起的前庭丧失 (NIVL) 的生理基础
- 批准号:
9109951 - 财政年份:2016
- 资助金额:
$ 15.6万 - 项目类别:
Neural Activity in Guinea Pig Vestibular Nuclei During Volitional Head Movements
意志头部运动期间豚鼠前庭核团的神经活动
- 批准号:
8690016 - 财政年份:2013
- 资助金额:
$ 15.6万 - 项目类别:
Neural Activity in Guinea Pig Vestibular Nuclei During Volitional Head Movements
意志头部运动期间豚鼠前庭核团的神经活动
- 批准号:
8582918 - 财政年份:2013
- 资助金额:
$ 15.6万 - 项目类别:
Vestibulo-Collic Reflex: A Quantitative Assay of Vestibular Function in Aging Mic
前庭结肠反射:老化麦克风前庭功能的定量测定
- 批准号:
7386164 - 财政年份:2007
- 资助金额:
$ 15.6万 - 项目类别:
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