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: 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
• 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

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与年龄相关的听力损失 (ARHL) 或 老年性耳聋。 ARHL 是排名第一的沟通障碍和排名第一的神经退行性疾病 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进步的影响 听觉敏感性下降，并且难以理解噪音中的言语。虽然 ARHL 是前三名之一 老年人的慢性疾病，目前尚无批准的医疗方法可预防或预防 逆转永久性听力损失（ARHL 或其他类型）。尽管经过数十年的研究和发现， 通过预防和治疗克服 ARHL 障碍仍然是一项重大科学任务 和临床挑战。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点是 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老化听觉系统的功能变化。我们 使用一系列动物和人类测量技术来确定 ARHL 的主要后果 科目。从评估当前理论模型和特定项目假设中获得的见解将 在指导新的行为、技术和医学治疗的发展方面发挥着重要作用 减缓或预防 ARHL 的进展。 具体目标 1. 确定激素补充可以在多大程度上预防或减缓 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 将与行为、生理和分子指标（包括外周指标）一起进行定量测量 和中枢听力测量，用于接受醛固酮激素治疗的老年受试者。 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长期、受控的暴露于 在动物饲养环境的自由场中呈现特定的人工生成的声音（鼠标 动物园设施）和通过人类定制的耳级听力仪器。结果指标将指数化 ARHL 关键特征和生物标志物的外围和中心组成部分。 具体目标 3. 确定老年人和动物的大脑可塑性与 ARHL 之间的关系， 包括所涉及的神经和分子机制。 实验方法：我们将在表明减少中枢抑制和/或塑性的工作的基础上 皮质活动的变化是 ARHL 的关键组成部分。实验的一个主要焦点将是链接 ARHL 与中枢神经抑制和兴奋之间的关系，特别是在老年人类和动物受试者中。

项目成果

Hybrid Electro-Plasmonic Neural Stimulation with Visible-Light-Sensitive Gold Nanoparticles.

使用可见光敏感金纳米颗粒进行混合电等离子体神经刺激。

• 发表时间: 2020-09-22
• 影响因子: 17.1
• 作者: Damnjanovic, Ratka;Bazard, Parveen;Frisina, Robert D;Bhethanabotla, Venkat R
• 通讯作者: Bhethanabotla, Venkat R

Humans detect gaps in broadband noise according to effective gap duration without additional cues from abrupt envelope changes.

人类根据有效间隙持续时间来检测宽带噪声中的间隙，而无需来自突然包络变化的额外提示。

• 发表时间: 2002-12
• 作者: Allen, Paul D;Virag, Tracy M;Ison, James R
• 通讯作者: Ison, James R

Micro-molded cannulae for intracochlear infusions in small rodents.

用于小型啮齿动物耳蜗内输注的微模制插管。

• 发表时间: 2007
• 作者: Johnson, Dean G;Zhu, Xiao Xia;Frisina, Robert D;Borkholder, David A
• 通讯作者: Borkholder, David A

Pre- but not post-menopausal female CBA/CaJ mice show less prepulse inhibition than male mice of the same age.

绝经前而非绝经后的雌性 CBA/CaJ 小鼠表现出比同龄雄性小鼠更少的前脉冲抑制。

• 发表时间: 2007-12-28
• 影响因子: 2.7
• 作者: Ison, James R;Allen, Paul D
• 通讯作者: Allen, Paul D

In-plane biocompatible microfluidic interconnects for implantable microsystems.

用于可植入微系统的面内生物相容性微流体互连。

• 发表时间: 2011-04
• 作者: Johnson, Dean G;Frisina, Robert D;Borkholder, David A
• 通讯作者: Borkholder, David A