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）：噪音创伤仍然是世界各地听力损失的主要原因。这项探索性拨款是基于噪音引起的听力损失的昼夜节律变化的新发现。听觉系统的昼夜节律究竟是如何被控制的尚不清楚。要测试的假设是，耳蜗有一个内在的生物钟，可以调节听觉系统对噪音创伤的敏感性。