The effect of noise induced hearing loss on Alzheimer's disease development and progression

噪音引起的听力损失对阿尔茨海默病发生和进展的影响

基本信息

批准号：
10661373
负责人：
Hong-Bo Zhao
金额：
$ 243.4万
依托单位：
YALE UNIVERSITY
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：
2023-04-15 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10661373
关键词：
APP-PS1 Acceleration Acoustic Stimulation Acoustics Age Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer&apos s disease patient Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Amyloid Auditory Auditory Evoked Potentials Auditory system Brain Clinical Trials Cochlea Communication Dementia Detection Development Devices Disease Progression Economics Environmental Risk Factor Foundations Goals Hair Cells Health Hearing Protection Hearing Tests Human Impaired cognition Impairment Inner Hair Cells Memory Memory Loss Morphology Mus Nerve Degeneration Neurodegenerative Disorders Neurons Noise Noise-Induced Hearing Loss Outer Hair Cells Photic Stimulation Play Population Predisposition Prevalence Purinoceptor Reporting Risk Factors Role Signal Transduction Social isolation Speech Speed Startle Reaction Stress Synapses System Testing Therapeutic Therapeutic Intervention Time Transgenic Organisms behavior test deafness epidemiology study hearing impairment hidden hearing loss high risk improved mouse model neuroinflammation neuropathology noise exposure noise pollution novel novel therapeutic intervention otoacoustic emission patch clamp preventive intervention rapid growth social spiral ganglion

项目摘要

Summary Alzheimer's disease (AD) is a common neurodegenerative disease characterized by a progressive loss of memory and cognitive decline. Over the last decade, the prevalence of AD and AD-related dementia (ADRD) has been rapidly growing. It is predicted that there will be 150 million AD patients by the year 2050, tripling the number in 2018. This will cause severe economic and social burdens. It has been estimated that speeding up the onset of dementia by even one year would increase the worldwide prevalence of dementia by 10%. However, currently, little is known about causes or mechanisms for this rapid increase in AD population. Many factors, particularly environmental factors, have been proposed as potential contributors to this rapid increase. Noise is a common high-risk environmental factor for human health and also a common deafness factor. Noise can induce hearing loss; hearing loss can induce and accelerate cognitive decline. In particular, recent studies demonstrate that noise can induce hidden hearing loss (HHL), which is caused by noise-induced inner hair cell synapse degeneration leading to difficulty of speech understanding in communication and therefore eventually social isolation. Currently, our world is becoming more and more noisy due to traffic, TV, and wide use of personal audio and video devices. We hypothesize that noise is a high-risk factor for AD development and may play an important role in AD population growing. To test this novel hypothesis, we will investigate whether noise can accelerate AD development and progression in AD mice (Aim 1). We will also investigate whether AD can impair the cochlear efferent system, which plays a critical role in the protection of hearing from noise, to increase susceptibility to noise and in turn to accelerate AD development and progression (Aim 2). In Aim 3, we will further investigate whether deficiency of ATP-purinergic function can accelerate AD development and progression, since our previous study found that deficiency of ATP-purinergic signaling function could induce hearing loss and increase susceptibility to noise. ATP-purinergic signaling also plays an important role in neuroinflammation, which is a consequence of noise exposure and plays a critical role in AD development and progression. Therefore, ATP-purinergic receptors have been considered an excellent potential target as well for AD prevention and treatment after anti-amyloid clinical trials have failed. These proposed studies will help to identify high-risk factors or contributors to the rapidly growth of the AD population and elucidate underlying mechanisms, thereby laying the foundation for development of new preventive and therapeutic interventions for AD and ADRD. Particularly, recent studies reported that visual and auditory stimulations with gamma oscillation cycles could reduce Aȕ expression in the brain and improve memory in AD mice, further indicating that the auditory system has a critical role in AD development and progression.

概括阿尔茨海默病（AD）是一种常见的神经退行性疾病，其特征是神经元逐渐丧失在过去的十年中，AD 和 AD 相关痴呆症 (ADRD) 的流行。预计到 2050 年，AD 患者将达到 1.5 亿，是这一数字的三倍。预计2018年将造成严重的经济和社会负担。即使痴呆症发作一年，全球痴呆症患病率也会增加 10%。然而，目前对于 AD 人口快速增加的原因或机制知之甚少。一些因素，特别是环境因素，被认为是造成这一快速增长的潜在因素。噪声是危害人类健康的常见高危环境因素，也是常见的耳聋因素。可以诱发听力损失；听力损失可以诱发并加速认知能力下降。证明噪音可以诱发隐性听力损失（HHL），这是由噪音诱导的内毛细胞引起的突触退化导致沟通中言语理解困难，因此最终目前，由于交通、电视和广泛使用，我们的世界变得越来越嘈杂。我们勇敢地承认，噪音是 AD 发展的高风险因素，并且可能会导致 AD 发展。为了检验这一新假设，我们将研究是否在 AD 人口增长中发挥重要作用。噪音是否可以加速 AD 小鼠的 AD 发展和进展（目标 1）。 AD 会损害耳蜗传出系统，而耳蜗传出系统在保护听力免受噪音影响方面发挥着至关重要的作用，增加对噪音的敏感性，进而加速 AD 的发展和进展（目标 2）。我们将进一步研究ATP嘌呤能功能的缺乏是否会加速AD的发展以及由于我们之前的研究发现 ATP 嘌呤能信号传导功能的进展可以诱导听力损失和对噪音的敏感性增加也起着重要作用。神经炎症，这是噪音暴露的结果，在 AD 的发展和因此，ATP 嘌呤能受体也被认为是一个极好的潜在靶点。这些拟议的研究将有助于抗淀粉样蛋白临床试验失败后的 AD 预防和治疗。识别 AD 人群快速增长的高风险因素或促成因素，并阐明潜在的原因机制，从而为开发新的预防和治疗干预措施奠定基础特别是对于 AD 和 ADRD，最近的研究报道了伽马射线的视觉和听觉刺激。振荡周期可以减少 AD 小鼠大脑中 Aş 的表达并改善记忆力，进一步表明听觉系统在 AD 的发生和发展中起着至关重要的作用。