Trophic interactions in developing and adult inner ear

发育中和成人内耳的营养相互作用

基本信息

  • 批准号:
    6445095
  • 负责人:
  • 金额:
    $ 34.58万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2002
  • 资助国家:
    美国
  • 起止时间:
    2002-02-15 至 2006-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Neuronal degeneration is a key determinant of impairment in many disorders of hearing and balance, and neuronal survival after hair cell loss is critical to the success of cochlear implants. Recent collaboration between our laboratories has suggested a role for the trophic factor neuregulin (NRG), and its receptors, the erbB family of tyrosine kinase receptors, in the normal development, proliferation and post-natal survival of hair cells and their sensory innervation. We developed a transgenic mouse in which normal NRG-erbB signaling is disrupted in the ear. Phenotypic analysis revealed a hearing disorder associated with post-natal, primary degeneration of cochlear nerve fibers (without hair cell loss) and a balance disorder associated with a reduction in the size of the vestibular sensory epithelium and the vestibular ganglion. Based on this transgenic mouse, the first cochlear model of primary post-natal neuronal degeneration, we hypothesize that NRG released by sensory neurons binds to erbB receptors on supporting cells in both cochlear and vestibular epithelia. In the cochlea, we hypothesize that NRG-erbB signaling causes support cells to release neurotrophins, e.g. NT-3, which, in turn, promote neuronal survival. In vestibular organs, we hypothesize that NRG-erbB signaling causes support-cell and hair-cell proliferation which indirectly promotes neuronal survival. This proposal combines expertise in cellular and molecular studies of neuronal development and survival with expertise in morpho-physiological characterization of ear disorders to test and refine these hypotheses concerning the role of NRG-erbB signaling in inner ear development and maintenance. Specific aims use a combination of light and electron-microscopic morphometry, immunohistochemistry, in situ hybridization, quantitative RT-PCR and tissue culture to analyze the spatial and temporal expression patterns of key molecules in this signaling pathway (Aim 1); investigate, both in vivo and in vitro, the role of NRG-erbB signaling in the cochlea (Aim 2) and vestibular organs (Aim 3), and analyze the roles of NRG in the interactions between supporting cells and sensory neurons, using co-cultures. Completion of these aims will clarify important cellular and molecular mechanisms underlying the normal development and survival of hair cells and neurons in the inner ear. Results may help in devising treatments to prevent or retard neuronal degeneration and/or induce hair cell proliferation in sensorineural ear disorders.
描述(由申请人提供):神经元变性是一个关键的决定因素

项目成果

期刊论文数量(0)
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Gabriel Corfas其他文献

Gabriel Corfas的其他文献

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{{ truncateString('Gabriel Corfas', 18)}}的其他基金

Michigan Otolaryngology Research Education (MORE)
密歇根耳鼻喉科研究教育(更多)
  • 批准号:
    10721751
  • 财政年份:
    2023
  • 资助金额:
    $ 34.58万
  • 项目类别:
The Roles of Neuronal Activity in Peripheral Nerve Myelination
神经元活动在周围神经髓鞘形成中的作用
  • 批准号:
    10375469
  • 财政年份:
    2020
  • 资助金额:
    $ 34.58万
  • 项目类别:
The Roles of Neuronal Activity in Peripheral Nerve Myelination
神经元活动在周围神经髓鞘形成中的作用
  • 批准号:
    10604374
  • 财政年份:
    2020
  • 资助金额:
    $ 34.58万
  • 项目类别:
Symposia for Association for Research in Otolaryngology
耳鼻喉科研究协会研讨会
  • 批准号:
    10570958
  • 财政年份:
    2019
  • 资助金额:
    $ 34.58万
  • 项目类别:
Symposia for Association for Research in Otolaryngology
耳鼻喉科研究协会研讨会
  • 批准号:
    10350692
  • 财政年份:
    2019
  • 资助金额:
    $ 34.58万
  • 项目类别:
Trophic interactions in developing and adult inner ear
发育中和成人内耳的营养相互作用
  • 批准号:
    7000360
  • 财政年份:
    2002
  • 资助金额:
    $ 34.58万
  • 项目类别:
Trophic Interactions in Developing and Adult Inner Ear
发育中和成人内耳的营养相互作用
  • 批准号:
    7713536
  • 财政年份:
    2002
  • 资助金额:
    $ 34.58万
  • 项目类别:
Trophic Interactions in Developing and Adult Inner Ear
发育中和成人内耳的营养相互作用
  • 批准号:
    8956510
  • 财政年份:
    2002
  • 资助金额:
    $ 34.58万
  • 项目类别:
Trophic Interactions in Developing and Adult Inner Ear
发育中和成人内耳的营养相互作用
  • 批准号:
    8388009
  • 财政年份:
    2002
  • 资助金额:
    $ 34.58万
  • 项目类别:
Trophic interactions in developing and adult inner ear
发育中和成人内耳的营养相互作用
  • 批准号:
    6622301
  • 财政年份:
    2002
  • 资助金额:
    $ 34.58万
  • 项目类别:

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