Anatomy of the Auditory System
听觉系统的解剖
基本信息
- 批准号:7640548
- 负责人:
- 金额:$ 30.14万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1979
- 资助国家:美国
- 起止时间:1979-07-01 至 2011-06-30
- 项目状态:已结题
- 来源:
- 关键词:AbbreviationsAcousticsAffectAffinityAnatomyAnimal ModelAnimalsAnteriorAntibodiesAuditory systemBrainBrain-Derived Neurotrophic FactorCellsChinchilla (genus)Cochlear nucleusCytologyDataDiseaseDorsalElectron MicroscopyEquilibriumEvaluationEventExposure toFGFR1 geneFibroblast Growth FactorFibroblast Growth Factor 2GABA ReceptorGlutamate ReceptorGlutamate TransporterGlutamatesGrowthHair CellsHistocytochemistryHistologicHyperactive behaviorHyperacusisImmunoelectron MicroscopyInbred MouseInhibitory SynapseInjuryInterneuronsLateralLeadLightLocationMicroscopicModelingMolecularMorphologyMusNMDA receptor A1Nerve Growth Factor ReceptorsNeuronsNeuropilNeurotrophic Tyrosine Kinase Receptor Type 2NoiseNoise-Induced Hearing LossPlasticsPlayPopulationProceduresProcessProgress ReportsProgressive DiseaseProteinsQuality of lifeRecoveryResearchResearch PersonnelRestRoleSiteStructureSynapsesSynaptic VesiclesTestingTimeTinnitusTransgenic MiceVariantbasefallsgephyrinimmunocytochemistrylight microscopyneurotrophic factornew growthnoise induced deafnesspostsynapticprogramsreceptorresearch study
项目摘要
DESCRIPTION (provided by applicant): Noise-induced hearing loss is an incurable, often progressive disease that impairs the quality of life. This project, using animal models, has provided evidence for degeneration of synaptic endings in the brain, besides loss of cochlear hair cells, as a major factor in this disease. This research offers preliminary data that the balance between excitatory and inhibitory endings in the cochlear nucleus shifts over time towards excitation and hyperactivity. The overall hypothesis is that these shifts provide a structural basis for tinnitus and hyperacusis after noise exposure. The project will characterize the degenerative process, at the cell and molecular levels, and trace changes in synaptic organization, including the exciting discovery that new synapses can form after the initial damage. The experiments aim to uncover factors that protect synapses or promote recovery after noise. Light and electron microscopy are used to examine damage in the cochlear nucleus of mice. Changes in the proportion of excitatory and inhibitory endings will be quantitated over 1-120 days after noise exposure. Synaptic vesicle histochemistry with light microscopy will show the numbers and locations of endings. Electron microscopy will show the proportion of endings with excitatory or inhibitory cytology using stereological approaches to test the hypothesis. Immunocytochemistry by light and electron microscopy will identify molecules underlying these changes. Transmitter-related molecules, including excitatory and inhibitory receptors and transporters, will be localized to specific types of neurons and synapses and tracked over the survival period. These data will pinpoint where and when in the cochlear nucleus an excitotoxic process may occur in cells. Neurotrophic factors and receptors will be identified and localized to indicate a role for trophic mechanisms. The role of fibroblast growth factor will be evaluated in a transgenic mouse that over expresses this factor. The hypothesis is that this factor protects against damage, and neurotrophins promote new growth of synapses. The results should lead to proposals for new therapies.
描述(由申请人提供):噪声性听力损失是一种无法治愈的,通常是渐进性的疾病,会损害生活质量。该项目使用动物模型,提供了证据,证明除了耳蜗毛细胞的损失之外,大脑中突触末梢的退化是这种疾病的主要因素。这项研究提供了初步的数据,耳蜗核兴奋性和抑制性终末之间的平衡随着时间的推移向兴奋和过度活跃的方向转变。总的假设是,这些变化提供了噪声暴露后耳鸣和听觉过敏的结构基础。该项目将在细胞和分子水平上表征退化过程,并跟踪突触组织的变化,包括令人兴奋的发现,即新的突触可以在最初的损伤后形成。这些实验旨在揭示保护突触或促进噪音后恢复的因素。用光学和电子显微镜检查小鼠耳蜗核的损伤。将在噪声暴露后1-120天内定量兴奋性和抑制性末梢比例的变化。光学显微镜下的突触囊泡组织化学将显示末端的数量和位置。电子显微镜将显示兴奋或抑制细胞学的比例使用体视学方法来检验假设。通过光学和电子显微镜的免疫细胞化学将确定这些变化背后的分子。与递质相关的分子,包括兴奋性和抑制性受体和转运蛋白,将定位于特定类型的神经元和突触,并在存活期内进行跟踪。这些数据将精确定位耳蜗核中细胞中兴奋性毒性过程可能发生的位置和时间。神经营养因子和受体将被确定和定位,以表明营养机制的作用。将在过表达该因子的转基因小鼠中评价成纤维细胞生长因子的作用。该假说认为,这种因子可以防止损伤,神经营养因子促进突触的新生长。研究结果应该会带来新疗法的建议。
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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DONALD KENT MOREST其他文献
DONALD KENT MOREST的其他文献
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{{ truncateString('DONALD KENT MOREST', 18)}}的其他基金
ANATOMY OF COCHLEAR NUCLEUS--CORRELATION WITH PHYSIOLOGY
耳蜗核的解剖结构--与生理学的相关性
- 批准号:
6104415 - 财政年份:1996
- 资助金额:
$ 30.14万 - 项目类别:
CELLULAR BASIS FOR SIGNAL PROCESSING IN AUDITORY SYSTEMS
听觉系统信号处理的细胞基础
- 批准号:
2014456 - 财政年份:1992
- 资助金额:
$ 30.14万 - 项目类别:
CELLULAR BASIS FOR SIGNAL PROCESSING IN AUDITORY SYSTEMS
听觉系统信号处理的细胞基础
- 批准号:
2126430 - 财政年份:1992
- 资助金额:
$ 30.14万 - 项目类别:
CELLULAR BASIS FOR SIGNAL PROCESSING IN AUDITORY SYSTEMS
听觉系统信号处理的细胞基础
- 批准号:
2126429 - 财政年份:1992
- 资助金额:
$ 30.14万 - 项目类别:
CELLULAR BASIS FOR SIGNAL PROCESSING IN AUDITORY SYSTEM
听觉系统信号处理的细胞基础
- 批准号:
3094889 - 财政年份:1992
- 资助金额:
$ 30.14万 - 项目类别:
CELLULAR BASIS FOR SIGNAL PROCESSING IN AUDITORY SYSTEMS
听觉系统信号处理的细胞基础
- 批准号:
2126431 - 财政年份:1992
- 资助金额:
$ 30.14万 - 项目类别:
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