Age-related Structural Analyses Core

年龄相关结构分析核心

• 批准号: 9340064
• 负责人: Michael Anne NMI Gratton
• 金额: $ 17.45万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9340064
• 关键词: Acquired Deafness; Affect; Age; Aging; Appropriateness Review; Archives; Auditory; Basilar Membrane; Biochemical; Biological; CBA/CaJ Mouse; Cell physiology; Cells; Collaborations; Color; Communication Disability; Complex; Confocal Microscopy; Data; Data Analyses; Data Collection; Electron Microscope; Electron Microscopy; Elements; Endolymph; Epithelial; Epithelial Cells; Epithelium; Etiology; Event; Exhibits; Experimental Designs; Extravasation; Freeze Fracturing; Genes; Genetic; Genetic Models; Genetic Transcription; Goals; Hair Cells; Hearing; Human; Imagery; Imaging Techniques; Inbred CBA Mice; Ion Channel; Knowledge; Label; Labyrinth; Lateral; Left; Location; Membrane; Membrane Potentials; Mission; Modeling; Molecular; Molecular Analysis; Mus; Mutant Strains Mice; Mutation; Myelin Sheath; National Institute on Aging; Nerve; Nerve Degeneration; Neurons; Neurosciences; Organ of Corti; Organelles; Output; Pathology; Perilymph; Presbycusis; Prevalence; Process; Property; Proteins; Research; Research Personnel; Resolution; Resources; Scheme; Scientist; Sensorineural Hearing Loss; Sensory; Services; Source; Specimen; Staining method; Stains; Structure; Synapses; Technology; Temporal bone structure; Tight Junctions; Tissue imaging; Tissues; Transcend; Transmission Electron Microscopy; age related; aged; design; digital imaging; electron tomography; hearing impairment; innovation; microscopic imaging; mouse model; neuromechanism; occludin; postsynaptic neurons; programs; protein expression; reconstruction; relating to nervous system; restoration; spiral ganglion; tissue preparation; transmission process

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.

项目概要 国家老龄化研究所的使命包括阐明老龄化的原因和治疗 年龄相关性听力损失（ARHL）是与衰老相关的最常见疾病之一。 事实上，患有 ARHL 的人数超过了任何其他获得性听力损失的人数。 这种衰老病理学的普遍存在是一个令人信服的指标，表明需要确定其深层机制 ARHL 并提供可以缓解沟通障碍的综合策略。 普遍的观点表明 ARHL 的病因是衰老的神经机制所固有的。 退化作为 ARHL 的一个持续特征，在档案人类颞骨分析中大量存在，这提供了 针对螺旋神经节神经元（SGN）的令人信服的理由本申请的总体目标。 旨在研究感音神经性 ARHL 的早期启动机制，并提出治疗途径 听觉功能的恢复。 核心 C 的目的是支持项目 1 至 3，以推进细胞和细胞领域的知识发展。 第八神经的分子神经科学水平，其突触，柯蒂氏器的输入细胞和细胞体 Rosenthal 根管 Core C 的任务是评估毛细胞 SGN 与年龄相关的超微结构变化。 SG 细胞中的突触以及第 8 神经的柯蒂氏器中紧密连接的完整性。 主要项目中进行的 SGC 和 HC 功能通过高分辨率和/或超微结构得到增强 为此，项目研究人员可以获取综合的生物样本特征。 Core C 的服务包括全面的电子显微镜和成像技术。 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 作为听觉周边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。 核心服务允许集中提供显微镜和数字成像服务。 通过高质量的电子显微镜进行复杂的组织制备和随后的染色 技术人员与精通冷冻断裂和电子断层扫描的科学家合作确保 核心总监使用经典和尖端技术进行一致的数据收集。 已采用适当的实验设计和数据分析。 结构分析确保资源在用户之间得到公平和公正的分配。