Roles of the Synapse in Hair-Cell Pathology
突触在毛细胞病理学中的作用
基本信息
- 批准号:10801270
- 负责人:
- 金额:$ 50.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-07-17 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:AMPA ReceptorsAcoustic NerveAddressAfferent NeuronsAgingAutomobile DrivingBiological AssayBiological ModelsCalciumCell physiologyCochleaDataDevelopmentEarExocytosisExposure toFishesFunctional ImagingFundingGlutamate ReceptorGlutamatesGoalsHair CellsHearingHourHumanImageImmunofluorescence ImmunologicImpairmentInflammationInflammatory ResponseInjuryInnate Immune SystemInner Hair CellsKnock-outLoudnessMacrophageMaintenanceMammalsMembrane PotentialsMetabolic stressMitochondriaModelingMolecularMorphologyN-Methyl-D-Aspartate ReceptorsN-MethylaspartateNerve DegenerationNoiseOrganPathologyPermeabilityPhagocytesPharmacologyPlayRecoveryRecovery of FunctionResearchRoleSensory ReceptorsSignal PathwaySiteStimulusStudy modelsSynapsesSynaptic VesiclesTestingTimeTraumaVisualizationWorkZebrafishcholinergicdefined contributionexcitotoxicitygain of functiongenetic manipulationglutamatergic signalinghearing impairmentinjuredlateral linemechanotransductionmitochondrial metabolismnerve repairnerve supplynoise exposureorgan repairpharmacologicpostsynapticpresynapticpreventrecruitreinnervationrepairedribbon synapsesynaptic inhibitionsynaptogenesistherapeutic target
项目摘要
Project Summary
Noise exposure damages synaptic connections between cochlear inner hair cells and innervating auditory
nerves. Data from mammalian models and humans indicate that loss of some inner hair cell synapses can be
permanent, leading to the slow degeneration of detached auditory nerves. Yet recent research also supports
that the mammalian cochlea possesses the intrinsic capacity for hair cell synaptic repair following noise
damage. Defining the cellular mechanisms of synapse repair following traumatic noise is a critical step toward
identifying therapeutic targets to promote repair of hair cell synaptic contacts and prevent loss of auditory
nerves.
The overall goal of this proposal is to understand the molecular basis of morphological and functional hair cell
organ repair and recovery following noise-induced damage. Current gaps in our understanding of how hair cell
synapses repair following traumatic noise are in large part due to our inability to define the cellular processes
that promote synaptic repair in mammalian model systems. This project will circumvent these issues by
investigating mechecaniclly induced hair-cell synapse loss and subsequent repair in the zebrafish lateral line—
a mechanosensory organ which is made up of clusters of innervated hair cells. Zebrafish lateral-line hair cells
are comparable to mammalian hair cells at the molecular and cellular level, including a shared mechanism of
hair cell synapse loss and de-innervation following traumatic overstimulation. Yet lateral line hair cells rapidly
and unambiguously repair lost synaptic connections within hours following stimulus-induced damage. Aim 1 of
our proposal will test the hypothesis that hair cell activity governs synaptic repair, while Aim 2 will define the
contribution of inflammation to synaptic recovery and reinnervation. The results of each of our Aims will provide
information on how hair cell synaptic connections are restored following traumatic overstimulation and will help
identify strategies to promote endogenous repair in noise exposed cochlea, thereby preventing subsequent
auditory nerve degeneration and hearing loss.
项目总结
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish.
- DOI:10.7554/elife.69264
- 发表时间:2021-10-19
- 期刊:
- 影响因子:7.7
- 作者:Holmgren M;Ravicz ME;Hancock KE;Strelkova O;Kallogjeri D;Indzhykulian AA;Warchol ME;Sheets L
- 通讯作者:Sheets L
Lateral line ablation by ototoxic compounds results in distinct rheotaxis profiles in larval zebrafish.
- DOI:10.1038/s42003-023-04449-2
- 发表时间:2023-01-21
- 期刊:
- 影响因子:5.9
- 作者:
- 通讯作者:
Using the Zebrafish Lateral Line to Understand the Roles of Mitochondria in Sensorineural Hearing Loss.
- DOI:10.3389/fcell.2020.628712
- 发表时间:2020
- 期刊:
- 影响因子:5.5
- 作者:Holmgren M;Sheets L
- 通讯作者:Sheets L
How Zebrafish Can Drive the Future of Genetic-based Hearing and Balance Research.
- DOI:10.1007/s10162-021-00798-z
- 发表时间:2021-06
- 期刊:
- 影响因子:0
- 作者:Sheets L;Holmgren M;Kindt KS
- 通讯作者:Kindt KS
Transmission Disrupted: Modeling Auditory Synaptopathy in Zebrafish.
- DOI:10.3389/fcell.2018.00114
- 发表时间:2018
- 期刊:
- 影响因子:5.5
- 作者:Kindt KS;Sheets L
- 通讯作者:Sheets L
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