SELECTING BIOMARKERS FOR THE MOLECULAR DIAGNOSIS OF SLEEPINESS

选择用于嗜睡分子诊断的生物标志物

• 批准号: 7498520
• 负责人: PAUL J SHAW
• 金额: $ 19万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-20 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7498520
• 关键词: Acute; Address; Age; Animal Model; Attention; Basic Science; Beds; Behavior; Biological; Biological Markers; Circadian Rhythms; Clinic; Clinical; Cognitive deficits; Communities; Condition; Consensus; Continuous Positive Airway Pressure; Coronary heart disease; Daily; Data Set; Databases; Diagnosis; Disease; Drosophila genus; Drosophila melanogaster; Endocrine; Evaluation; General Population; Genes; Genetic; Genetic Markers; Goals; Health; Homologous Gene; Hour; Human; Hypoxia; Immunology; Individual; Invasive; Life; Liquid substance; Messenger RNA; Metabolism; Molecular Diagnosis; Monitor; Names; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Obstructive Sleep Apnea; Occupational Accidents; Outcome; Patients; Polymerase Chain Reaction; Population; Predisposition; Procedures; Proteins; Public Health; Reporting; Research; Risk; Saliva; Sampling; Sleep; Sleep Apnea Syndromes; Sleep Deprivation; Sleep Disorders; Societies; Testing; Time; Translating; Treatment Efficacy; day; experience; fly; human subject; tool; trafficking; vigilance

DESCRIPTION (provided by applicant): It is a common experience to sacrifice sleep to meet the demands of our 24-h society. Current estimates reveal that, as a society, we sleep on average 2 h less than we did 40 years ago. This level of sleep restriction results in negative health outcomes and is sufficient to produce cognitive deficits, reduced attention, and is associated with increased risk for traffic and occupational accidents. Unfortunately, there is no simple quantifiable marker that can detect an individual who is excessively sleepy before adverse outcomes become evident. To address this issue we have developed a simple and effective strategy for identifying biomarkers of sleepiness using genetic and pharmacological tools that dissociate sleep drive from wake time in the model organism Drosophila melanogaster. In this proposal we will choose select genes from our Drosophila Database of Biomarkers to develop a noninvasive tool that can be used for the molecular diagnosis of sleepiness in humans. We will identify genes that are responsive to acute sleep loss then determine if these biomarkers are altered in patients with obstructive sleep apnea syndrome.PROJECT NARRATIVE Sleep loss adversely effects metabolic processes, endocrine functions, and immunology and may increase the susceptibility of individuals to serious diseases, including obesity, type II diabetes and coronary heart disease to name a few. Developing tools for the molecular diagnosis of sleepiness will assist with the identification and treatment of sleepiness in the general population and in critical patient populations.

描述(申请人提供)：牺牲睡眠来满足我们24小时社会的需求是一种常见的经验。目前的估计显示，作为一个社会，我们的平均睡眠时间比40年前减少了2小时。这种程度的睡眠限制会导致负面的健康后果，并足以产生认知缺陷、注意力下降，并与交通和职业事故的风险增加有关。不幸的是，没有一个简单的可量化的标记可以在不良后果变得明显之前检测出一个人过度困倦。为了解决这个问题，我们开发了一种简单而有效的策略来识别嗜睡的生物标记物，使用遗传和药理学工具，在模式生物果蝇黑腹果蝇中分离睡眠驱动和醒来时间。在这项提议中，我们将从我们的果蝇生物标志物数据库中选择精选基因来开发一种非侵入性工具，可以用于人类嗜睡的分子诊断。我们将确定对急性睡眠缺失有反应的基因，然后确定这些生物标记物在阻塞性睡眠呼吸暂停综合征患者中是否发生改变。 睡眠不足对代谢过程、内分泌功能和免疫学产生不利影响，并可能增加个人对严重疾病的易感性，包括肥胖症、II型糖尿病和冠心病等。开发嗜睡的分子诊断工具将有助于在普通人群和危重病人群体中识别和治疗嗜睡。