Role of Histamine in Narcolepsy/EDS Disorders

组胺在发作性睡病/EDS 疾病中的作用

• 批准号: 7186303
• 负责人: SEIJI NISHINO
• 金额: $ 7.83万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-19 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7186303
• 关键词: Affect; Anger; Animal Model; Animals; Applications Grants; Area; Breeding; Canis familiaris; Cataplexy; Clinical; Collection; Condition; Data; Data Set; Disease; Emotional; Excessive Daytime Sleepiness; Functional disorder; General Population; Genes; Genetic; Goals; HLA Antigens; Histamine; Human; Hypersomnias; Hypersomnolence; Hypnagogic Hallucination; Idiopathic Hypersomnolence; Japanese Population; Labrador; Laughter; Measures; Mediating; Modeling; Muscle; Mutation; Narcolepsy; Neuraxis; Neuropeptides; Numbers; Obstructive Sleep Apnea; Patients; Penetrance; Pharmacotherapy; Play; Polysomnography; Primary Insomnia; Puncture procedure; REM Sleep; Reporting; Research; Research Design; Research Priority; Research Project Grants; Restless Legs Syndrome; Role; Sampling; Secondary Insomnia; Secondary to; Severities; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep Paralysis; Source; Syndrome; Time; Work; alertness; autosomal recessive trait; cost; day; design; healthy volunteer; hypocretin; neurophysiology; novel; prepro-orexin; prospective; receptor; transmission process

DESCRIPTION (provided by applicant): Role of Histamine in Narcolepsy/EDS Disorders R03 small research grants are designed for short-term, high impact, low cost studies. The goal of this proposed work is to extend on preliminary data indicating low CSF histamine levels in disorders of excessive daytime sleepiness. We will also study diurnal fluctuation in CSF histamine levels in normal, healthy volunteers. An increasing number of animal studies suggest that histamine plays a major role in regulating alertness. This may be relevant to narcolepsy since hypocretin stimulates histaminergic transmission and narcoleptic canines with deficient hypocretin transmission also have low central nervous histamine contents. We also have preliminary data from two sources (our own samples and from a Japanese collaborator) indicating low CSF histamine in human narcolepsy-cataplexy with hypocretin deficiency. Most interestingly however, we also found decreased CSF histamine in a subset of patients with daytime sleepiness, but in the context of normal hypocretin levels, for example with idiopathic hypersomnia. Patients with daytime sleepiness associated with sleep apnea had normal levels. This exciting preliminary result suggests that histamine may play a role in the pathophysiology of non-hypocretin dependent syndrome of centrally- mediated hypersomnolence. Our goal will be to extend this dataset using a large number of existing CSF samples. We will also conduct exploratory statistical analysis to study clinical predictors of low CSF histamine levels. Whether or not this change is primary or secondary to daytime sleepiness in these patients will be explored by further grant applications once the preliminary finding is confirmed and additional exploratory analysis have been conducted. As almost nothing is known on the pathophysiology of non- hypocretin deficient hypersomnias, we believe this work to be ideally suited for a small grant application.

描述（由申请人提供）：组胺在睡病/EDS疾病中的作用R03小型研究补助金的设计用于短期，高影响力，低成本研究。这项建议的工作的目的是扩展初步数据，表明白天过度嗜睡的疾病中CSF组胺水平较低。我们还将研究正常健康志愿者中CSF​​组胺水平的昼夜波动。越来越多的动物研究表明，组胺在调节警觉中起着重要作用。这可能与睡病有关，因为低载素会刺激缺乏降压素传播的组胺能传播和毒素犬，也具有低中枢神经组胺含量。我们还获得了来自两个来源（我们自己的样本和日本合作者）的初步数据，这些数据表明人类发作性发育不全且缺乏症中的人性发作性疾病 - 疾病 - 痛苦中的CSF组胺低。但是，最有趣的是，我们还发现白天嗜睡的一部分中CSF组胺降低，但在正常的低载素水平的情况下，例如特发性性高感觉。与睡眠呼吸暂停相关的白天嗜睡患者的水平正常。这一令人兴奋的初步结果表明，组胺可能在中心介导的性超善的非甲状腺果仁蛋白依赖性综合征的病理生理学中起作用。我们的目标是使用大量现有的CSF样本扩展此数据集。我们还将进行探索性统计分析，以研究低CSF组胺水平的临床预测因子。一旦确认了初步发现并进行了其他探索性分析，这是这些患者白天嗜睡的主要还是继发于白天嗜睡的主要或继发。由于非降压素缺乏性高血压症的病理生理学几乎没有任何了解，因此我们认为这项工作非常适合小型赠款应用。