Mechanisms of hypersensitivity to sound-induced cochlear damage
对声音引起的耳蜗损伤过敏的机制
基本信息
- 批准号:9764613
- 负责人:
- 金额:$ 60.32万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-03-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AMPA ReceptorsAcousticsAddressAge-MonthsAgingAndrogensAttentionBiochemicalBiological FactorsCa(2+)-Transporting ATPaseCastrationCochleaCochlear NerveComplexConfocal MicroscopyDataEndoplasmic ReticulumEnvironmentEstradiolEstrogen ReceptorsEstrogensExhibitsFemaleFiberFrequenciesGlutamate ReceptorGlutamatesGonadal HormonesGonadal Steroid HormonesHearingHormonesHourHumanHypersensitivityImmunohistochemistryInner Hair CellsIschemiaKnock-outKnockout MiceLabyrinthLeadLinkMeasuresMediatingMolecularMusNeuronsNoiseOvarianOvarian hormonePathogenesisPhosphorylationPositioning AttributeProcessPublishingPumpQuantitative Reverse Transcriptase PCRRoleSensorySex DifferencesSignal TransductionStructureSurfaceSwellingSynapsesSynaptic TransmissionSystemTestingWestern Blottingauditory pathwaybasechildhood hearing lossexcitotoxicityhearing impairmentmalemutantnerve supplyneurotoxicitypostsynapticprotective effectreceptorreceptor functionribbon synapsesexual dimorphismsoundspiral gangliontraffickingtransmission process
项目摘要
Project Summary
All information about the acoustic environment is carried from the inner ear to the CNS by the afferent fibers of
the cochlear nerve. Rapidly gating AMPA glutamate receptors (AMPAR; GluA2, GluA3 and GluA4 subunits)
mediate synaptic transmission at the mature synapse between the inner hair cells (IHC) and the afferent fibers
of the cochlear nerve (IHC synapse). However, the contribution of each type of AMPAR subunit to overall
glutamatergic receptor function and afferent transmission/sensitivity in the cochlea is poorly understood.
Understanding this process is important because glutamate excitotoxicity through AMPAR has been implicated
in the pathogenesis of hearing loss caused by noise, ischemia and aging. Sex differences in the vulnerability to
hearing loss occur in humans. We therefore began investigating the contribution of AMPAR subunits to
transmission at the IHC synapse and whether there are sex-specific differences in AMPAR subunits that
contribute to sound-induced cochlear damage and hearing loss. Based on functional and ultrastructural
preliminary data, we now hypothesize that “GluA3 AMPAR subunits have a critical role in the sexually
dimorphic vulnerability to hearing loss”. To define mechanistically how GluA3 contributes to the structural and
molecular components of IHC synapses and to sex differences that underlie the hypersensitivity to sound-
induced cochlear damage, we will use a powerful combination of functional (ABRs, DPOAEs),
immunocytochemical (confocal microscopy), biochemical, qRT-PCR, and ultrastructural approaches to test the
following hypotheses. In Aim 1, we will determine whether GluA3 promotes the abundance of GluA2 at IHC
synapses. In Aim 2, we will determine whether GluA3 at IHC synapses protects mice from sound-induced
cochlear damage. Aim 3, based on published data and our preliminary findings, we propose the hypothesis
that in the absence of GluA3, ovarian hormones facilitate the hypersensitivity to sound-induced cochlear
damage, while androgens have protective effects. These proposed studies are the first to address the
important question of how changes in AMPAR subunit composition lead to sex differences in hearing loss.
项目总结
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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Maria Eulalia Rubio其他文献
Maria Eulalia Rubio的其他文献
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{{ truncateString('Maria Eulalia Rubio', 18)}}的其他基金
Alterations and mechanisms of auditory information processing in the aging auditory pathway
衰老听觉通路中听觉信息处理的改变和机制
- 批准号:
10496287 - 财政年份:2023
- 资助金额:
$ 60.32万 - 项目类别:
Mechanisms of hypersensitivity to sound-induced cochlear damage
对声音引起的耳蜗损伤过敏的机制
- 批准号:
10670814 - 财政年份:2013
- 资助金额:
$ 60.32万 - 项目类别:
Mechanisms of hypersensitivity to sound-induced cochlear damage
对声音引起的耳蜗损伤过敏的机制
- 批准号:
10442553 - 财政年份:2013
- 资助金额:
$ 60.32万 - 项目类别:
Mechanisms of hypersensitivity to sound-induced cochlear damage
对声音引起的耳蜗损伤过敏的机制
- 批准号:
9914229 - 财政年份:2013
- 资助金额:
$ 60.32万 - 项目类别:
Anatomical and Functional Properties of Auditory Nerve Synapses
听神经突触的解剖和功能特性
- 批准号:
8620649 - 财政年份:2013
- 资助金额:
$ 60.32万 - 项目类别:
Anatomical and Functional Properties of Auditory Nerve Synapses
听神经突触的解剖和功能特性
- 批准号:
8804940 - 财政年份:2013
- 资助金额:
$ 60.32万 - 项目类别:
Anatomical and Functional Properties of Auditory Nerve Synapses
听神经突触的解剖和功能特性
- 批准号:
8477668 - 财政年份:2013
- 资助金额:
$ 60.32万 - 项目类别:
Anatomical and Functional Properties of Auditory Nerve Synapses
听神经突触的解剖和功能特性
- 批准号:
9207101 - 财政年份:2013
- 资助金额:
$ 60.32万 - 项目类别:
Mechanisms of hypersensitivity to sound-induced cochlear damage
对声音引起的耳蜗损伤过敏的机制
- 批准号:
10200747 - 财政年份:2013
- 资助金额:
$ 60.32万 - 项目类别:
Anatomical and Functional Properties of Auditory Nerve Synapses
听神经突触的解剖和功能特性
- 批准号:
8810723 - 财政年份:2013
- 资助金额:
$ 60.32万 - 项目类别:
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