Neurology, University of Missouri, Harry S. Truman Memorial Veterans Hospital, Research, Room A023, 800 Hospital Drive, Columbia, MO 65210, USA.
Sleep Med Rev. 2011 Feb;15(1):65-74. doi: 10.1016/j.smrv.2010.06.004. Epub 2010 Sep 20.
The histaminergic system is exclusively localized within the posterior hypothalamus with projection to almost all the major regions of the central nervous system. Strong and consistent evidence exist to suggest that histamine, acting via H₁ and/or H₃ receptor has a pivotal role in the regulation of sleep-wakefulness. Administration of histamine or H₁ receptor agonists induces wakefulness, whereas administration of H₁ receptor antagonists promotes sleep. The H₃ receptor functions as an auto-receptor and regulates the synthesis and release of histamine. Activation of H₃ receptor reduces histamine release and promotes sleep. Conversely, blockade of H₃ receptor promotes wakefulness. Histamine release in the hypothalamus and other target regions is highest during wakefulness. The histaminergic neurons display maximal activity during the state of high vigilance, and cease their activity during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The cerebrospinal levels of histamine are reduced in diseased states where hypersomnolence is a major symptom. The histamine deficient L-histidine decarboxylase knockout (HDC KO) mice display sleep fragmentation and increased REM sleep during the light period along with profound wakefulness deficit at dark onset, and in novel environment. Similar results have been obtained when histamine neurons are lesioned. These studies strongly implicate the histaminergic neurons of the TMN to play a critical role in the maintenance of high vigilance state during wakefulness.
组胺能系统仅局限于下丘脑后部，投射到中枢神经系统的几乎所有主要区域。有强有力且一致的证据表明，组胺通过 H₁ 和/或 H₃ 受体发挥作用，在调节睡眠-觉醒方面起着关键作用。给予组胺或 H₁ 受体激动剂可诱导觉醒，而给予 H₁ 受体拮抗剂则促进睡眠。H₃ 受体作为自受体，调节组胺的合成和释放。激活 H₃ 受体可减少组胺释放并促进睡眠。相反，阻断 H₃ 受体可促进觉醒。下丘脑和其他靶区的组胺释放在觉醒时最高。在高警觉状态下，组胺能神经元显示出最大的活性，并在非快速眼动（NREM）和快速眼动（REM）睡眠期间停止其活动。在以过度嗜睡为主要症状的疾病状态下，脑脊液中的组胺水平降低。缺乏组胺的 L-组氨酸脱羧酶敲除（HDC KO）小鼠在光照期间表现出睡眠片段化和 REM 睡眠增加，以及在黑暗开始时和新环境中严重的觉醒缺陷。当组胺神经元被损伤时，也得到了类似的结果。这些研究强烈表明 TMN 的组胺能神经元在维持觉醒时的高警觉状态中起着关键作用。
