Determinants of age-induced hearing loss and reversal strategies

年龄引起的听力损失的决定因素和逆转策略

基本信息

批准号：
10496280
负责人：
EBENEZER N YAMOAH
金额：
$ 238.49万
依托单位：
UNIVERSITY OF NEVADA RENO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10496280
关键词：
3-Dimensional Ablation Address Age Aging Analytical Chemistry Anatomy Animal Model Animal Sources Animals Auditory Auditory Brainstem Responses Auditory area Axon Behavioral Biochemical Biological Markers Biology Brain Brain Stem Calcium Cell Nucleus Chronology Clinical Cochlear nucleus Code Complex Demyelinations Dimensions Electrophysiology (science)Ensure Equilibrium Etiology Event Exhibits Functional disorder Genetic Genetic Models Hair Cells Human Image Imaging Techniques Individual Joints Knock-in Label Labyrinth Lead Life Expectancy Medial Mental Depression Modeling Molecular Myelin Nature Neurons Noise-Induced Hearing Loss Organelles Outcome Pathology Personal Satisfaction Pharmacogenetics Phenotype Physiology Presbycusis Productivity Proteome Proteomics Psychological Impact Public Health Pyramidal Tracts Research Personnel Resources Sampling Sensorineural Hearing Loss Sensory Social isolation Societies Sum Synapses Synaptic plasticity Testing Time Work age related aged aging auditory system auditory pathway clinically relevant design effective therapy functional plasticity hearing impairment in vivo insight mouse model neural neural network neuron loss optogenetics programs signal processing sound spiral ganglion stem tool trapezoid body treatment strategy

项目摘要

Abstract Presbycusis or age-related hearing loss (ARHL) represents the most prevalent sensory deficit. It begets social isolation and depression. We hypothesize that aging auditory neurons undergo cellular, and structural changes, resulting in demyelination and selective neuronal subtypes loss. The ensuing plasticity produces profound neural network re-wiring and aberrant functional plasticity along the auditory pathway. These predicted changes' progressive nature requires systematic analyses of the ARHL mechanism at different auditory pathway hubs, which can only be achieved through a joint collaborative effort. Motivated by this public health challenge, we have designed a collaborative multiscale study that addresses the aging auditory system's successive mechanisms. The clinical and translational outcomes of our findings promise to be vast. The overarching hypotheses are tested in three Projects, using resources and tools from four Cores. The investigative team consists of experts from genetic to physiology and imaging and analytical chemistry. Three projects (P1-3) are served by four Cores (A-D). Core A is for administrative oversight and organization of the Cores and Projects. The team includes Drs. Yamoah (Project 1), Xie (Project 2), Maria-Rubio/Williamson (Project 3), Yamoah (Core A), Yamoah/Lee (Core B), Fritzsch/Perkins (Core C), and Zhu (Core D). Together, they will determine the mechanisms of ARHL of sensory and neural etiology. The team has worked together synergistically and productively. The projects focus on critical centers of the auditory pathways recognized for the coding and processing of sound information. They include the primary auditory neurons (AN; P1), cochlear nuclei (CN; P2-3), superior olivary complex (SOC; P2-3), and auditory cortex (ACtx, P3). We use genetic, optogenetics, and pharmacogenetic mouse models (Core B). We employ structural analyses (Core C) and differential proteomic analyses of young-and aged-auditory neurons to uncover biomarkers (Core D). Integration of the program ensures outcomes that are overwhelmingly greater than the sum of the individual components. Identification of ARHL biomarkers is likely to pave the way for effective treatment strategies.

抽象的老年性耳聋或与年龄相关的听力损失（ARHL）是最普遍的感觉缺陷。它产生社交孤立和抑郁。我们假设衰老的听觉神经元经历细胞和结构变化，导致脱髓鞘和选择性神经元亚型丧失。随之而来的可塑性产生了深刻的神经网络重新布线和听觉通路上异常的功能可塑性。这些预测的变化' 渐进性需要对不同听觉通路中枢的 ARHL 机制进行系统分析，这只有通过共同努力才能实现。受到这一公共卫生挑战的激励，我们设计了一项协作性多尺度研究，解决衰老听觉系统的连续性问题机制。我们的研究结果有望产生巨大的临床和转化成果。首要的使用来自四个核心的资源和工具在三个项目中测试假设。研究小组由遗传学、生理学、成像和分析化学领域的专家组成。三个项目（P1-3）由四个核心（A-D）服务。核心A是行政监督和组织核心和项目。该团队包括博士。 Yamoah（项目 1）、Xie（项目 2）、Maria-Rubio/Williamson （项目 3）、Yamoah（核心 A）、Yamoah/Lee（核心 B）、Fritzsch/Perkins（核心 C）和 Zhu（核心 D）。一起，他们将确定 ARHL 的感觉和神经病因机制。团队一起努力协同且富有成效。这些项目侧重于公认的听觉通路的关键中心声音信息的编码和处理。它们包括初级听觉神经元（AN；P1）、耳蜗核（CN；P2-3）、上橄榄复合体（SOC；P2-3）和听觉皮层（ACtx，P3）。我们利用基因，光遗传学和药物遗传学小鼠模型（核心 B）。我们采用结构分析（核心 C）和对年轻和老年听觉神经元进行差异蛋白质组分析以发现生物标志物（核心 D）。计划的整合确保了结果远远大于个人的总和成分。 ARHL 生物标志物的鉴定可能为有效的治疗策略铺平道路。