Hearing circadian rhythms.

聆听昼夜节律。

• 批准号: 8489380
• 负责人: BARBARA CANLON
• 金额: $ 13.52万
• 依托单位: KAROLINSKA INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-15 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8489380
• 关键词: Acoustic Trauma; Adrenal Glands; Adrenalectomy; Affect; Animals; Auditory; Auditory system; Basic Science; Biological Clocks; Chimeric Proteins; Circadian Rhythms; Clinical; Clinical Sciences; Clock protein; Cochlea; Cochlear nucleus; Collection; Corticosterone; Effectiveness; Environment; Feedback; Genes; Glucocorticoids; Grant; Hearing; Hearing problem; Hormonal; Human; Hypothalamic structure; Inferior Colliculus; Inflammatory Response; Knockout Mice; Light; Location; Luciferases; Mediating; Messenger RNA; Metabolism; Methods; Molecular; Mus; Noise; Noise-Induced Hearing Loss; Output; Pathway interactions; Pattern; Periodicity; Peripheral; Physiological; Pituitary Gland; Play; Population; Predisposition; Public Health; Reaction; Reporter; Research; Role; Signal Transduction; Sleep; Steroids; Stress; Structure; System; Techniques; Testing; Time; Tissues; Transgenic Mice; Trauma; Travel; Variant; base; circadian pacemaker; clinically relevant; feeding; hearing impairment; hypothalamic-pituitary-adrenal axis; knockout animal; novel; public health relevance; repaired; research study; response; suprachiasmatic nucleus

DESCRIPTION (provided by applicant): Noise trauma continues to be a major cause for hearing loss throughout the world. This exploratory grant is based on the novel finding showing a circadian variation in noise-induced hearing loss. Exactly how this circadian rhythm in the auditory system is controlled is not known. The hypothesis to be tested is that the cochlea has an intrinsic circadian clock that modulates the sensitivity of the auditory system to noise trauma. This project seeks to determine the underlying functional and molecular mechanisms underlying this new finding. The suprachiasmatic nucleus (SCN) is the master clock that synchronizes and coordinates rhythms to regulate physiological functions including metabolism, inflammatory responses, feeding, sleep-wake patterns and the hypothalamic pituitary adrenal (HPA axis). The SCN and/or the HPA axis can be regulating the auditory clock or there is an internal clock in auditory tissues (cochlea, cochlear nucleus and inferior colliculus). Aim 1 will answer the fundamental question if circadian auditory oscillations and auditory sensitivity to trauma is controlled by central circadian pacemaker SCN, or these oscillations occur independently of the SCN. The second part of aim 1 will determine the role of the HPA axis and glucocorticoids in mediating the auditory circadian rhythm noise-induced damage. The assumption is that the SCN drives a circadian rhythm in glucocorticoid release and an intact SCN will not be effective if the output pathway is interrupted by adrenalectomy. These experiments will illustrate how and if glucocorticoids are involved in the entrainment of the auditory clock rhythmicity. The last part of aim 1 will be directly testing if the isolated auditory tissues (i.e. without influence of SCN or te HPA axis) have an intrinsic rhythm that regulates noise-induced damage. Aim 2 will determine the physiological and molecular effects of noise trauma on PER2 knockout mice to directly demonstrate the role of PER2 in regulating sensitivity to noise trauma at different times of the day. Aim 2 will also determine if protection and repair against noise trauma also has a circadian rhythm. Using functional and molecular techniques we will characterize the circadian effect of noise damage and protective mechanisms. These studies are of clinical importance since noise-induced hearing disorders are an important public health issue and are exponentially increasing in the human population. These novel findings will open new avenues of research and have important implications for both basic and clinical science.

描述（由申请人提供）：噪声创伤仍然是全世界听力损失的主要原因。该探索性赠款基于新的发现，该发现显示了噪声引起的听力损失的昼夜节律变化。尚不清楚听觉系统中的这种昼夜节律如何控制。要测试的假设是耳蜗具有固有的昼夜节律，可调节听觉系统对噪声创伤的敏感性。 该项目旨在确定这一新发现的基本功能和分子机制。超平子核（SCN）是同步和协调节奏以调节生理功能的主时钟，包括代谢，炎症反应，喂养，睡眠效果模式和下丘脑垂体肾上腺肾上腺（HPA轴）。 SCN和/或HPA轴可以调节听觉时钟，也可以在听觉组织（耳蜗，耳蜗核和下丘）中有一个内部时钟。 AIM 1将回答一个基本问题，如果昼夜节律的听觉振荡和对创伤的听觉敏感性由中央昼夜节律PAPEMAKER SCN控制，或者这些振荡独立于SCN。 AIM 1的第二部分将确定HPA轴和糖皮质激素在介导听觉昼夜节律噪声引起的损伤中的作用。假设是，SCN在糖皮质激素释放中驱动昼夜节律，如果输出途径被肾上腺切除术中断，完整的SCN将无效。这些实验将说明糖皮质激素如何以及是否涉及听觉时钟的节奏性。最后一部分 AIM 1将直接测试如果孤立的听觉组织（即SCN或TE HPA轴没有影响）具有固有的节奏，可以调节噪声诱导的损伤。 AIM 2将确定噪声创伤对PER2敲除小鼠的生理和分子作用，直接证明PER2在调节一天中不同时间对噪声创伤的敏感性中的作用。 AIM 2还将确定防止噪声创伤的保护和修复是否也具有昼夜节律。使用功能和分子技术，我们将表征噪声损伤和保护机制的昼夜节律效应。这些研究具有临床重要性，因为噪声引起的听力障碍是一个重要的公共卫生问题，并且人口的成倍增加。这些新颖的发现将开辟新的研究途径，并对基础科学和临床科学具有重要意义。