Structure-function analyses on novel processes of type II vestibular hair cells

II型前庭毛细胞新过程的结构功能分析

基本信息

批准号：
8691781
负责人：
Ruth Anne Eatock
金额：
$ 19.88万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8691781
关键词：
Adult Affect Aging American Animals Brain Calculi Cell Communication Cell Death Cell physiology Cells Cellular biology Cessation of life Code Communication Coupled Coupling Cytoplasm Dizziness Ear Economic Burden Electron Microscopy Elements Epithelium Equilibrium Eye Fiber Gap Junctions Gene Mutation Goals Hair Cells Head Movements Health Care Costs Hearing problem Indium Individual Infection Injection of therapeutic agent Injury Investigation Laboratories Labyrinth Lateral Lead Length Mammals Massachusetts Measures Mediating Membrane Molecular Molecular Profiling Morphology Movement Mus Natural regeneration Nerve Nerve Endings Operative Surgical Procedures Organ Pattern Pharmaceutical Preparations Phenotype Physiological Physiology Pilot Projects Play Process Property Quality of life Recovery Reporting Research Personnel Retina Rodent Role Sensory Shapes Signal Transduction Structure Supporting Cell Synapses Therapeutic Transmission Electron Microscopy Type II Hair Cell Universities Ursidae Family Vertigo Vestibular Hair Cells Vestibular Nerve Washington Whole-Cell Recordings afferent nerve base cell injury cell type equilibration disorder experience falls functional restoration functional status hair cell regeneration novel patch clamp postnatal premature public health relevance relating to nervous system research study signal processing transmission process

项目摘要

DESCRIPTION (provided by applicant): About 35% of Americans experience balance problems such as vertigo, lack of coordinated movements, and dizziness. Balance problems can severely reduce quality of life, add to high healthcare costs, and lead to premature death due to falls. A major cause of balance disorders is the loss of vestibular hair cells in the inner ear, which convert head movements into electrical signals that are sent to the brain via the vestibular nerve. Hair cell death has many causes, including gene mutation, injury, infection, therapeutic surgery and drug treatments, and aging. The proposed project brings together the expertise of two investigators who share the following goals: to understand the fundamental mechanisms underlying vestibular hair cell function and to develop ways to treat balance disorders resulting from hair cell injury or loss. The Stone lab at the University of Washington (UW) recently discovered that one type of vestibular hair cell - type II - in adult rodents has a feature that has never been described: one or more extensions of cytoplasm (or processes) that project laterally from the base of the cell, sometimes over several cell lengths. These processes have a variety of shapes and seem to contact other cells in the epithelium, including other type II hair cells. This latter observation raises the novel idea that direct communication between type II hair cells could modulate vestibular signaling. In addition, the Stone lab found that type II-lie hair cells with processes are the only hair cell type that is regenerated spontaneously in adult mouse vestibular epithelia after damage (Golub et al., 2012). In order to develop treatments for individuals with balance disorders, it is critical to define both the identity of spontaneously regenerated hair cells and the role that they play in vestibular processing. For this project, the Stone lab at UW and the Eatock lab at Harvard University propose to characterize the hair cell processes, to identify the hair cell type that bears them, and to begin to examine how these processes affect the coding of head movements and the transmission of sensory information from the inner ear to the brain. For both normal and regenerated states, the Stone lab will analyze morphological and molecular properties of hair cells with processes, while the Eatock lab will examine their physiological properties and define the types of connections that the processes make with nerves and other hair cells. Proposed studies in normal vestibular organs are essential steps in defining the structure of the novel processes and their functions in vestibular processing. Confirmation of hair cell-hair cell communication would transform our understanding of hair cell biology by allowing the possibility of lateral interactions as documented in the retina. Studies of damaged vestibular organs will help uncover the relationship between normal and regenerated hair cells with processes and the potential of regenerated hair cells to restore function in balance and hearing disorders.

描述（由申请人提供）：大约 35% 的美国人有平衡问题，例如眩晕、动作不协调和头晕。平衡问题会严重降低生活质量，增加高昂的医疗费用，并导致因跌倒而过早死亡。平衡障碍的一个主要原因是内耳前庭毛细胞的丧失，这些毛细胞将头部运动转化为电信号，通过前庭神经发送到大脑。毛细胞死亡的原因有很多，包括基因突变、损伤、感染、治疗性手术和药物治疗以及衰老。拟议的项目汇集了两位研究人员的专业知识，他们有以下共同目标：了解前庭毛细胞功能的基本机制，并开发治疗因毛细胞损伤或损失而导致的平衡障碍的方法。华盛顿大学 (UW) 的 Stone 实验室最近发现，成年啮齿动物中的一种前庭毛细胞（II 型）具有从未被描述过的特征：细胞质（或过程）的一个或多个延伸，从侧面突出细胞的底部，有时超过几个细胞的长度。这些突起具有多种形状，并且似乎与上皮中的其他细胞接触，包括其他 II 型毛细胞。后一种观察提出了一种新颖的想法，即类型之间的直接通信 II 毛细胞可以调节前庭信号传导。此外，Stone 实验室发现，具有突起的 II 型毛细胞是成年小鼠前庭上皮损伤后唯一能自发再生的毛细胞类型（Golub 等，2012）。为了开发针对患有平衡障碍的个体的治疗方法，定义自发再生毛细胞的身份及其在前庭处理中所发挥的作用至关重要。在这个项目中，威斯康星大学的斯通实验室和哈佛大学的伊托克实验室建议描述毛细胞过程的特征，识别承载它们的毛细胞类型，并开始研究这些过程如何影响头部运动的编码和感觉信息从内耳传输到大脑。对于正常状态和再生状态，Stone 实验室将分析毛细胞及其过程的形态和分子特性，而 Eatock 实验室将检查其生理特性并定义这些过程与神经和其他毛细胞的连接类型。对正常前庭器官的拟议研究是定义新过程的结构及其在前庭处理中的功能的重要步骤。毛细胞-毛细胞通讯的确认将通过允许视网膜中记录的横向相互作用的可能性来改变我们对毛细胞生物学的理解。对受损前庭器官的研究将有助于揭示正常毛细胞和再生毛细胞之间的关系，以及再生毛细胞恢复平衡和听力障碍功能的潜力。