Aging and Dysfunction in the Peripheral Vestibular System

周围前庭系统的衰老和功能障碍

• 批准号: 10840176
• 负责人: Anthony Wei Peng
• 金额: $ 1.28万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-05 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10840176
• 关键词: Acceleration; Action Potentials; Address; Adult; Age; Aging; Animal Behavior; Behavior; Behavioral; Brain; Cell Count; Cell physiology; Cells; Cochlea; Dendrites; Development; Elderly; Electrophysiology (science); Epithelium; Equilibrium; Evoked Potentials; Exhibits; Fiber; Functional disorder; Gerbils; Glutamates; Hair; Hair Cells; Head; Head Movements; Human; Immunohistochemistry; Impairment; Laboratories; Labyrinth; Mediating; Morphology; Motion; Mus; Nerve Fibers; Organ; Patients; Pattern; Performance; Peripheral; Persons; Physiological; Population; Positioning Attribute; Potassium Channel; Preparation; Presbycusis; Presynaptic Terminals; Principal Investigator; Process; Property; Reflex action; Reporting; Rodent; Rodent Model; Sensory; Shapes; Signal Pathway; Signal Transduction; Stimulus; Synapses; Synaptic Cleft; Synaptic Transmission; System; Techniques; Testing; Type I Hair Cell; Type II Hair Cell; Utricle structure; Vestibular Hair Cells; Work; afferent nerve; age related; aged; cell type; effective therapy; electrical property; equilibration disorder; experience; falls; mechanotransduction; nerve supply; noise exposure; novel; novel therapeutics; otoconia; ototoxicity; postnatal; postsynaptic; receptor; response; ribbon synapse; therapy development; transmission process; virtual; voltage clamp; young adult

Project Summary Vestibular dysfunction becomes more prevalent with age and it is estmated that more than 80% of people over 80 years old experience dysfunction5. Furthermore, approximately 8 million adults in the US suffer from balance impairment due to damage to the peripheral vestibular system, but effective treatments for balance dysfunction are virtually non-existent. Vestibular hair cells within vestibular canal and otolith organs convert hair bundle motion into receptor potentials and sensory information is relayed to the brain by action potentials in vestibular afferent nerves. Afferents in central zones of vestibular neuroepithelia exhibit different responses to vestibular stimuli than afferents in peripheral zones. There are three types of vestibular afferents: calyx-only afferents innervate one or more type I hair cells, bouton dendrites innervate type II hair cells and dimorphic afferents contact both hair cell types. Calyx-only afferents are present only in central zones and have irregular firing patterns, whereas dimorphic afferents exist in both zones and have regular firing patterns. We will study age-related dysfunction in calyx-bearing afferents in gerbil vestibular organs using novel preparations developed in the laboratories of the principal investigators. We will use electrophysiological, hair bundle stimulation, immunohistochemical and behavioral approaches to address age-related changes in mature and aged vestibular epithelia. In Aim 1 we will determine if functional changes in vestibular hair cell mechanotransduction and/or basolateral currents occur with age. Aim 2 will test the hypotheses that synaptic degeneration of calyx terminals will manifest as morphological uncoupling of type I hair cells from their associated calyces and deficits in vestibular evoked responses and behaviors. In Aim 3 we will directly investigate changes at the type I hair cell/calyx synapse by recording spontaneous activity and responses to hair bundle stimulation in mature and aged calyx afferents. Our investigative team is uniquely positioned to carry out the proposed studies. Results from this work will provide new information on how the aging process impacts peripheral vestibular signals and may inform development of vestibular neurotherapeutics targeting afferent nerves in order to restore normal vestibular function.

项目摘要 前庭功能障碍随着年龄的增长而变得更加普遍，因此，超过80％的人超过了 80岁的经验功能障碍5。此外，美国约有800万成年人遭受 由于外围前庭系统损坏而导致的平衡损伤，但有效的治疗方法 功能障碍实际上不存在。前庭毛细胞和耳石器官转换 束束运动进入受体电位，并通过动作电位将感官信息传递到大脑 在前庭传入神经中。前庭神经上皮中央区域中的传入表现出不同的反应 在外围区域中的传入比前庭刺激。有三种类型的前庭传入：仅花萼 传入一个或多个I型毛细胞，胸花树突支配II型毛细胞和双态 传入与两种毛细胞类型接触。仅在钙毛的传入中仅存在于中央区域，并且有不规则的传入 射击模式，而二态传入都存在于两个区域中，并且具有常规的射击模式。我们将学习 使用新型制剂 在主要研究人员的实验室中开发。我们将使用电生理，头发束 刺激，免疫组织化学和行为方法，以解决与年龄相关的成熟和成熟变化的变化 老年前庭上皮。在AIM 1中，我们将确定前庭毛细胞的功能变化是否变化 机械转导和/或基底外侧电流随着年龄的增长而发生。 AIM 2将检验突触的假设 花萼末端的变性将表现为I型毛细胞的形态解偶联 相关的钙和前庭诱发反应和行为的缺陷。在AIM 3中，我们将直接 通过记录自发活动和对 成熟和老化的花萼传入中的头发束刺激。我们的调查团队独特地定位 进行拟议的研究。这项工作的结果将提供有关衰老过程的新信息 影响周围的前庭信号，并可能为靶向前庭神经疗法的发展提供信息 传入神经以恢复正常的前庭功能。