GDNF Protection in the Inner Ear

GDNF 对内耳的保护

• 批准号: 6464176
• 负责人: YEHOASH RAPHAEL
• 金额: $ 30.87万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6464176
• 关键词: audiometry; auditory pathways; behavior test; biological models; cell type; ear hair cell; electrophysiology; gene delivery system; gene expression; glia; immunocytochemistry; in situ hybridization; laboratory mouse; labyrinth; microarray technology; morphology; neuroprotectants; neurotrophic factors; noise biological effect; protein localization; sensory signal detection; transfection /expression vector; transmission electron microscopy; trauma; vestibular pathway

DESCRIPTION (provided by applicant): Inner ear lesions result in permanent deficiencies in balance and hearing. It is therefore important to reduce or eliminate the lesions that are accompanied by a variety of insults to the inner ear. Neurotrophic factors have been shown to protect inner ear structure and function against acoustic and ototoxic trauma. One neurotrophic factor, the Glial cell-line derived neurotrophic factor (GDNF) demonstrated a robust protective effect against trauma in the inner ear of the guinea pig. The experiments in this grant are designed to continue to characterize the protective effect of GDNF in the auditory and vestibular systems, and to extend the data to a different animal model, the mouse. The experiments will use gene transfer technology for GDNF transgene over-expression in the inner ear. Specifically, we propose to (a) determine the protective effect of GDNF on the mouse auditory and vestibular epithelia using electrophysiological, behavioral and morphological analyses, (b) determine the cells types that bind GDNF in normal and traumatized inner ear tissues and (c) shed light on the genes that are involved in the downstream signaling cascade of GDNF. The data we propose to generate will enhance our understanding of the mechanisms of action of GDNF in normal and injured inner ear epithelia, knowledge that may eventually lead to better clinical treatments

描述（由申请人提供）：内耳损伤导致永久性的 平衡和听力缺陷。因此，减少或 消除伴随各种内部损伤的病变 耳朵。 神经营养因子已被证明可以保护内耳结构和 具有抵抗声学和耳毒性创伤的功能。一种神经营养因子， 胶质细胞源性神经营养因子（GDNF）表现出强大的 对豚鼠内耳外伤有保护作用。这 这笔赠款中的实验旨在继续表征 GDNF 对听觉和前庭系统的保护作用，并延长 将数据传输给不同的动物模型——小鼠。 实验将使用基因转移技术进行GDNF转基因 内耳过度表达。具体来说，我们建议 (a) 确定 GDNF对小鼠听觉和前庭上皮细胞的保护作用 电生理学、行为学和形态学分析，(b) 确定 在正常和受伤的内耳组织中结合 GDNF 的细胞类型和 (c) 揭示参与下游信号级联的基因 GDNF。 我们建议生成的数据将增强我们对 GDNF 在正常和受损内耳上皮细胞中的作用机制， 最终可能带来更好的临床治疗的知识