NEUROTROPHINS AND AGING INNER EAR

神经营养因子和内耳老化

• 批准号: 6323331
• 负责人: LYNNE M. BIANCHI
• 金额: $ 18.14万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6323331
• 关键词: aging; cochlear nerve; developmental neurobiology; gerbil /jird; growth factor receptors; human tissue; labyrinth; neural degeneration; neurons; neurotrophic factors; protein tyrosine kinase; receptor expression; tissue /cell culture

Degeneration of spiral ganglion (cochlear) neurons is one of the most commonly observed changes in the aging inner ear. In humans and some animal species, neuronal degeneration occurs in the absence of sensory hair cell loss. One factor contributing to neuronal presbyacusis may be changes in the production of trophic molecules derived from sensory hair cells, ganglionic supporting cells or the neurons themselves. Several neurotrophic factors are expressed in the inner ear and members of the neurotrophin gene family are known to be critical for development of cochlear and vestibular neurons. To test the hypothesis that changes in neurotrophins and/or their associated receptors contribute to the age- related loss of neurons, a series of complementary experiments will be conducted using gerbil and human inner ear tissue. Aim 4.1 addresses the temporal and spatial expression of neurotrophins and their associated receptors using the reverse transcription polymerase chain reaction and in situ hybridization. Aim 4.2 evaluates the production of neurotrophin- like proteins using immunohistochemistry, in vitro assays of inner ear tissues and enzyme-linked immunoabsorbant assays. Aim 4.3 examines whether the survival or outgrowth of neuronal processes from young and aging cochlear neurons is influenced by exogenously applied neurotrophins or other inner ear-derived factors. Together, the proposed experiments will offer new sights into the role of neurotrophins in the aging inner ear as well as information regarding the therapeutic potential of neurotrophic molecules in preventing age-related hearing loss.

螺旋神经节（耳蜗）神经元的变性是最多的神经元之一 通常观察到内耳衰老的变化。 在人类和一些 动物物种，神经元变性发生在没有感觉的情况下 毛细胞损失。 导致神经元的一个因素可能是 从感觉头发得出的营养分子的产生变化 细胞，神经节支撑细胞或神经元本身。 一些 神经营养因素在内耳和成员中表达 众所周知，神经营养蛋白基因家族对于发展至关重要 耳蜗和前庭神经元。 检验的假设是变化 神经营养蛋白和/或其相关受体有助于年龄 神经元的相关损失，一系列互补实验将是 使用沙鼠和人内耳组织进行。 AIM 4.1解决 神经营养蛋白及其相关的时间和空间表达 使用逆转录聚合酶链反应的受体和 原位杂交。 AIM 4.2评估神经营养蛋白的产生 像使用免疫组织化学的蛋白质一样，内耳的体外测定 组织和酶连接的免疫反剂测定法。 AIM 4.3检查 是来自Young和的神经元过程的生存或产物 老化的耳蜗神经元受外源施用的神经营养蛋白的影响 或其他内耳衍生的因素。 共同提出的实验 将为神经营养蛋白在衰老内部的角色中提供新的景点 耳朵以及有关治疗潜力的信息 神经营养分子预防年龄相关的听力损失。