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

• 批准号: 9011244
• 负责人: Robert D Frisina
• 金额: $ 180.65万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9011244
• 关键词: Acoustics; Affect; Age; Aging; Aldosterone; Animal Model; Animals; Arthritis; Auditory; Auditory system; Behavioral; Biological Markers; Biological Neural Networks; Biological Response Modifier Therapy; Brain; Cardiovascular Diseases; Chronic; Clinical; Clinical Trials; Communication impairment; Custom; Development; Ear; Elderly; Environment; Evaluation; Exposure to; Goals; Hearing; High Prevalence; Hormonal; Hormones; Human; Intervention; Investigation; Lead; Link; Measurement; Measures; Medical; Methods; Molecular; Mus; Nerve Degeneration; Nervous system structure; Neural Inhibition; Neuronal Plasticity; Neurons; Noise; Outcome Measure; Peripheral; Pharmaceutical Preparations; Physiological; Play; Presbycusis; Prevention; Process; Research; Role; Serum; Speech; Supplementation; Techniques; Testing; Theoretical model; Therapeutic; Time; Work; age related; aged; aging population; base; catalyst; dosage; experience; hearing impairment; hormone therapy; human subject; improved; indexing; innovation; insight; instrument; novel; prevent; public health relevance; relating to nervous system; research study; response; sound; speech processing; young adult

 DESCRIPTION (provided by applicant): 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 application 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 ar 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.

 描述（由申请人提供）：我们的长期目标是改善年龄相关性听力损失（ARHL）或老年性耳聋的衰弱后果。ARHL是头号沟通障碍和头号神经退行性疾病，我们不断扩大的老龄化人口。绝大多数60岁以上的人都受到这种听觉灵敏度逐渐下降的影响，难以在噪音中理解言语。虽然ARHL是老年人的三大慢性疾病之一，但目前还没有批准用于预防或逆转永久性听力损失（ARHL或其他类型）的药物。尽管经过数十年的研究和发现，通过预防和治疗克服ARHL的障碍仍然是一个重大的科学和临床挑战。本申请的主题重点是通过生物治疗和神经可塑性的靶向诱导来调节老年性耳聋。这些方法的一个重要特点是阐明了听觉加工中外周功能和中枢听觉可塑性的相关作用。这项开创性的研究使用创新的催化剂来诱导衰老听觉系统的功能变化。我们使用一系列测量技术在动物和人类受试者中针对ARHL的主要后果。从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旨在减缓或预防ARHL进展的新行为，技术和医学治疗的发展方面发挥重要作用。具体目标1.确定激素补充剂可以预防或减缓ARHL进展的程度。实验方法：在接受醛固酮激素治疗的老年受试者中，将沿着行为、生理和分子指标（包括外周和中枢听力测量）定量测量血清醛固酮和其他相关指标和生物标志物。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在动物饲养环境（小鼠饲养设施）的自由场中以及通过人类的定制耳级听力仪器对特定人工生成的声音进行延长的受控暴露。结果指标将索引ARHL的关键特征和生物标志物的外周和中心成分。具体目标3。确定老年人和动物的大脑可塑性和ARHL之间的关系，包括所涉及的神经和分子机制。实验方法：我们将建立在工作表明，减少中央抑制和/或皮质活动的可塑性变化是ARHL的关键组成部分。实验的一个主要焦点将是ARHL和中枢神经抑制和兴奋之间的联系，特别是在老年人和动物受试者中。