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）：组胺在嗜睡症/EDS 疾病中的作用 R03 小额研究资助专为短期、高影响、低成本研究而设计。这项拟议工作的目标是扩展初步数据，表明白天过度嗜睡疾病中脑脊液组胺水平较低。我们还将研究正常健康志愿者脑脊液组胺水平的昼夜波动。越来越多的动物研究表明，组胺在调节警觉性方面发挥着重要作用。这可能与发作性睡病有关，因为下丘脑分泌素刺激组胺能传递，而下丘脑分泌素传递不足的发作性睡病犬的中枢神经组胺含量也较低。我们还从两个来源（我们自己的样本和日本合作者的样本）获得了初步数据，表明伴有下丘脑分泌素缺乏的嗜睡症猝倒症患者的脑脊液组胺水平较低。然而，最有趣的是，我们还发现，在部分白天嗜睡的患者中，脑脊液组胺减少，但下丘脑分泌素水平正常，例如特发性嗜睡症。与睡眠呼吸暂停相关的白天嗜睡的患者的水平正常。这一令人兴奋的初步结果表明，组胺可能在中枢介导的嗜睡的非下丘脑分泌素依赖性综合征的病理生理学中发挥作用。我们的目标是使用大量现有的 CSF 样本来扩展该数据集。我们还将进行探索性统计分析，以研究脑脊液组胺水平低的临床预测因素。一旦初步发现得到证实并进行了额外的探索性分析，这种变化是主要还是继发于这些患者的白天嗜睡，将通过进一步的拨款申请来探讨。由于对非下丘脑分泌素缺乏性睡眠过度的病理生理学几乎一无所知，我们相信这项工作非常适合小额资助申请。