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Aging Auditory System: Presbycusis and Its Neural Bases

听觉系统老化：老年性耳聋及其神经基础

基本信息

批准号：
10448661
负责人：
Robert D Frisina
金额：
$ 19.64万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10448661
关键词：
Acoustics Affect Age Aging Aldosterone Animals Arthritis Auditory Behavioral Biological Markers Biological Response Modifier Therapy Brain Cardiovascular Diseases Chronic Clinical Communication impairment Custom Development Ear Elderly Environment Evaluation Exposure to Goals Hearing High Prevalence Hormonal Human Intervention Lead Link Measurement Measures Medical Molecular Mus Nerve Degeneration Neural Inhibition Neuronal Plasticity Outcome Measure Peripheral Pharmaceutical Preparations Physiological Play Presbycusis Prevention Research Role Serum Speech Supplementation Techniques Testing Theoretical model Work aging auditory system aging population auditory processing base catalyst efficacy clinical trial experimental study hormone therapy human subject indexing innovation insight instrument novel permanent hearing loss prevent public health relevance relating to nervous system sound speech in noise

项目摘要

ABSTRACT/SUMMARY- Overall Our long-term goal is to ameliorate the debilitating consequences of age-related hearing loss (ARHL) or presbycusis. ARHL is the number one communication disorder and number one neurodegenerative condition of our expanding aging population. The vast majority of people over age 60 are affected by this progressive decline in auditory sensitivity and difficulty understanding speech in noise. While ARHL is one of the top three chronic medical conditions of the elderly, there currently are no approved medical treatments for preventing or reversing permanent hearing loss (ARHL or other types). Despite decades of research and discovery, overcoming the barriers of ARHL through prevention and treatment continues to represent a major scientific and clinical challenge. The thematic focus of this proposal is modulation of presbycusis through biotherapeutics and targeted induction of neural plasticity. An important feature of these approaches is elucidating the related roles of peripheral function and central auditory plasticity in auditory processing. This pioneering research uses innovative catalysts to induce functional changes in the aging auditory system. We target the primary consequences of ARHL using an array of measurement techniques in animal and human subjects. Insights gained from the evaluation of current theoretical models and project-specific hypotheses will play a prominent role in guiding development of new behavioral, technological and medical treatments aimed at slowing or preventing the progression of ARHL. Specific Aim 1. Determine the degree to which hormonal supplementation can prevent or slow the progression of ARHL. Experimental approach: Serum aldosterone and other related metrics and biomarkers will be quantitatively measured along with behavioral, physiological, and molecular indices, including peripheral and central hearing measures, in aging subjects undergoing aldosterone hormone therapies. Specific Aim 2. Determine the ability of enriched acoustic environments to ameliorate presbycusis. Experimental approach: Enriched acoustic environments will consist of extended, controlled exposure to specific artificially generated sounds presented in the free field in the animal holding environment (mouse vivarium facility) and via custom ear-level hearing instruments in humans. Outcome measures will index peripheral and central components of key features and biomarkers of ARHL. Specific Aim 3. Determine relations between brain plasticity and ARHL in older humans and animals, including the neural and molecular mechanisms that are involved. Experimental approach: We will build upon work indicating that reduced central inhibition and/or plastic changes in cortical activity are key components of ARHL. A major focus of experiments will be the link between ARHL and central neural inhibition and excitation, particularly in older human and animal subjects.

摘要/总结-总体我们的长期目标是改善年龄相关性听力损失（ARHL）或老年性耳聋ARHL是头号沟通障碍和头号神经退行性疾病我们不断增长的老龄化人口。绝大多数60岁以上的人都受到这种进步的影响。听觉灵敏度下降，在噪音中难以理解言语。虽然ARHL是前三名老年人的慢性疾病，目前还没有批准的预防或永久性听力损失（ARHL或其他类型）。尽管经过几十年的研究和发现，通过预防和治疗克服ARHL的障碍仍然是一项重要的科学研究，临床挑战。该提案的主题重点是通过以下方式调节老年性耳聋：生物治疗和神经可塑性的靶向诱导。这些方法的一个重要特征是阐明外周功能和中枢听觉可塑性在听觉处理中的相关作用。这开创性的研究使用创新的催化剂来诱导衰老的听觉系统的功能变化。我们在动物和人类中使用一系列测量技术，针对ARHL的主要后果科目从对当前理论模型和项目特定假设的评估中获得的见解将在指导新的行为、技术和医疗方法的发展方面发挥突出作用，减缓或阻止ARHL的进展。具体目标1。确定激素补充剂可以预防或减缓 ARHL的进展。实验方法：血清醛固酮和其他相关指标和生物标志物将沿着行为、生理和分子指标进行定量测量，包括外周和中枢听力测量，在接受醛固酮激素治疗的老年受试者中。具体目标2。确定丰富的声学环境改善老年性耳聋的能力。实验方法：丰富的声学环境将包括延长，受控暴露于在动物保持环境（小鼠）中的自由场中呈现的特定人工生成的声音动物园设施）和通过人类的定制耳级听力仪器。结果指标将索引 ARHL关键特征和生物标志物的外周和中心成分。具体目标3。确定老年人和动物大脑可塑性与ARHL之间的关系，包括相关的神经和分子机制实验方法：我们将建立在工作表明，减少中枢抑制和/或塑料皮质活动的变化是ARHL的关键组成部分。实验的一个主要重点将是 ARHL与中枢神经抑制和兴奋之间的关系，特别是在老年人和动物受试者中。

项目成果

期刊论文数量（130）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（5）

DOI：
10.1016/j.neuroscience.2013.11.058
发表时间：
2014-02-14
期刊：
Neuroscience
影响因子：
3.3
作者：
Tang X;Zhu X;Ding B;Walton JP;Frisina RD;Su J
通讯作者：
Su J

A novel BK channel-targeted peptide suppresses sound evoked activity in the mouse inferior colliculus.

DOI：
10.1038/srep42433
发表时间：
2017-02-14
期刊：
Scientific reports
影响因子：
4.6
作者：
Scott LL;Brecht EJ;Philpo A;Iyer S;Wu NS;Mihic SJ;Aldrich RW;Pierce J;Walton JP
通讯作者：
Walton JP

Effects of spectral modulation filtering on vowel identification.

频谱调制滤波对元音识别的影响。