Arousal effect of orexin A depends on activation of hte histmic system
Arousal effect of orexin A depends on activation of hte histmic system
复制标题
DOI：
10.1073/pnas.181330998
复制
发表时间：
2001-08-14
影响因子：
11.1
通讯作者：
Hayaishi, O
中科院分区：
文献类型：
--
作者：
Huang, ZL;Qu, WM;Hayaishi, O
食欲素神经元专门位于下丘脑外侧区域，并将其纤维投射到整个中枢神经系统，包括组胺能结节乳头核（TMN）。食欲素系统功能障碍会导致睡眠障碍发作性睡病，但食欲素在生理性睡眠-觉醒调节中的作用及其机制仍有待阐明。在这里，我们提供了几条证据表明食欲素 A 通过 TMN 和组胺 H-1 受体 (H1R) 诱导觉醒。通过微透析探针向大鼠 TMN 灌注食欲素 A（5 和 25 pmol/min）1 小时，开始灌注后 2 小时内的清醒度迅速分别增加 2.5 倍和 4 倍，同时快速眼动 (REM) 和非快速眼动睡眠减少。微透析研究表明，在 TMN 上应用食欲素 A，在 80 至 160 分钟内，内侧视前区和额叶皮层的组胺释放量增加了约 2 倍，持续时间为 80 至 160 分钟，呈剂量依赖性。此外，向小鼠侧脑室输注食欲素A（1.5 pmol/min）6小时，开始输注后8小时内的觉醒度显着增加，达到与野生型小鼠活跃期观察到的觉醒度相同的水平，但在H1R基因敲除小鼠中则完全没有。这些发现强烈表明，食欲素 A 的唤醒作用取决于 H1R 介导的组胺能神经传递的激活。
Orexin neurons are exclusively localized in the lateral hypothalamic area and project their fibers to the entire central nervous system, including the histaminergic tuberomammillary nucleus (TMN). Dysfunction of the orexin system results in the sleep disorder narcolepsy, but the role of orexin in physiological sleep-wake regulation and the mechanisms involved remain to be elucidated. Here we provide several lines of evidence that orexin A induces wakefulness by means of the TMN and histamine H-1 receptor (H1R). Perfusion of orexin A (5 and 25 pmol/min) for 1 hr into the TMN of rats through a microdialysis probe promptly increased wakefulness for 2 hr after starting the perfusion by 2.5-and 4-fold, respectively, concomitant with a reduction in rapid eye movement (REM) and non-REM sleep. Microdialysis studies showed that application of orexin A to the TMN increased histamine release from both the medial preoptic area and the frontal cortex by approximate to2-fold over the baseline for 80 to 160 min in a dose-dependent manner. Furthermore, infusion of orexin A (1.5 pmol/min) for 6 hr into the lateral ventricle of mice produced a significant increase in wakefulness during the 8 hr after starting infusion to the same level as the wakefulness observed during the active period in wild-type mice, but not at all in H1R gene knockout mice. These findings strongly indicate that the arousal effect of orexin A depends on the activation of histaminergic neurotransmission mediated by H1R.