Age-related Structural Analyses Core

项目摘要 国家老龄化研究所的使命包括阐明老龄化的原因和治疗方法， 衰老的各个方面听力损失（ARHL）是最常见的疾病之一， 衰老事实上，患有ARHL的人数超过了任何其他后天性听力损失。的 这种衰老病理学的流行是一个令人信服的指标，需要确定的深入机制， 并提供全面的策略，以减轻沟通障碍。的 流行的解释认为ARHL的病因是衰老的神经机制所固有的。神经元 退化作为ARHL的持续特征在人类颞骨分析档案中大量存在，提供了一个 靶向螺旋神经节神经元（SGN）的令人信服的理由。本申请的总体目的是 目的是研究感觉神经性ARHL的早期启动机制， 恢复听觉功能。 核心C的目的是支持项目1至3在蜂窝和 分子神经科学水平在第8神经，其突触，细胞的输入器官的Corti和细胞体， 罗森塔尔氏管核心C的使命是评估年龄相关的超微结构变化的毛细胞-SGN 突触，在SG细胞以及在Corti器官的紧密连接的完整性。第八神经的研究， 在主要项目中进行的SGC和HC功能通过高分辨率和/或超微结构增强 生物样本的特征。为此，项目调查人员可以获得综合的 核心C的服务，包括全面的电子显微镜和成像技术。这些 服务包括用于结构/超微结构分析的组织制备和图像采集服务， 作为听觉周围蛋白质的超微结构定位，从而使项目研究人员能够 专注于同一组织的创新细胞和分子分析。 核心服务允许显微镜和数字成像服务的集中来源。的 复杂组织制备的可用性以及随后通过高质量电子显微镜进行的染色 技术人员与精通冷冻断裂和电子断层扫描的科学家合作， 使用经典和尖端技术进行一致的数据收集。核心主任保证， 采用了适当的实验设计和数据分析。适当审查关于 结构分析确保在用户之间公平和公正地分配资源。

Project Summary The mission of the National Institute on Aging includes elucidation of the causes as well as treatment of all aspects of aging. Age-related hearing loss (ARHL) is one of the most common ailments associated with aging. In fact, the number of people with ARHL exceeds that of any other acquired hearing loss. The prevalence of this aging pathology is a compelling indicator of the need to identify the in-depth mechanisms of ARHL and to provide comprehensive strateties with which the communication disability can be alleviated. The prevailing account suggests that the etiology of ARHL is intrinsic to the neural mechanisms of aging. Neuronal degeneration as a persistent feature of ARHL abounds in archival human temporal bone analyses, providing a compelling rationale for targeting spiral ganglion neurons (SGN). The overall aims of the present application are to investigate the very early, initiating mechanisms of sensorineural ARHL and to propose avenues for restoration of auditory function. The purpose of Core C is to support Projects 1 through 3 in advancing knowledge, at the cellular and molecular neuroscience level in the 8th nerve, its synapses, cells of input in the organ of Corti and cell bodies in Rosenthal’s canal. Core C's mission is to assess age-related ultrastructural changes at the hair cell-SGN synapses, in the SG cell as well as the integrity of the tight junctions in the organ of Corti. Studies of 8th nerve, SGC and HC function conducted in the main Projects are enhanced by high resolution and/or ultrastructural characterizations of the biological specimen. To this end, the Project investigators have access to integrated services of Core C that include a comprehensive range of electron microscopy and imaging techniques. These services include tissue preparation and image acquisition services for structural/ultrastructural analysis as well as ultrastructural localization of proteins in the auditory periphery thus allowing the Project investigators to focus on innovative cellular and molecular analyses of the same tissue. The Core services allow a centralized source for microscopy and digital imaging services. The availability of complex tissue preparation and subsequent staining by a highly qualified electron microscope technician, collaboration with scientists well-versed in freeze-fracture and electron tomography assures consistent data collection using classical and cutting edge technology. The Core Director assures that the most appropriate experimental designs and data analysis have been utilized. Appropriate review of requests for structural analyses assures that there is a fair and equitable distribution of resources among users.