ABSTRACT

The well-known Two-Process Model of Sleep Regulation describes the integration of the circadian rhythm of arousal and sleep – Process C, and the homeostatic pressure to sleep – Process S. Presently, the known biological markers for Process C are melatonin and core body temperature; whereas, for Process S, there is no biological marker except that of aspects of the electroencephalogram (EEG). Endozepines are a class of endogenous compounds that act like benzodiazepines (BZ), i.e., serving as ligands for the BZ binding sites on GABA_A receptors. Not much is known about the role of endozepines, in particular non-peptide endozepines, in the sleep field except very few reports about high concentrations observed in endozepine stupor, a rare phenomenon of idiopathic recurring stupor. We focused on hypoxanthine and thromboxane A2, which are considered to have endozepine function. This study aimed to examine the effect of 24 h of acute sleep deprivation on blood levels of hypoxanthine and thromboxane A2 of healthy subjects without sleep problems or disorders. The results showed a significant decrease of both compounds in the morning after sleep deprivation in comparison to the unrestricted normal sleep condition, thereby suggesting that these endozepines are secreted regularly while asleep, and, thus, are necessary for the sleep process. This study is the first to suggest a connection between specific biological markers – endozepines and Process S – in the Two-Process Model of Sleep Regulation and, furthermore, it sheds light on the possible role of endozepines in sleepiness and fatigue.

摘要

著名的睡眠调节双过程模型描述了唤醒和睡眠的昼夜节律 - 过程 C 和睡眠稳态压力 - 过程 S 的整合。 目前，已知的过程 C 生物标志物是褪黑激素和核心体温度; 而对于过程 S，除了脑电图 (EEG) 的各个方面之外，没有其他生物标记。Endozepines 是一类内源性化合物，其作用类似于苯二氮卓类 (BZ)，即充当 GABA _A上 BZ 结合位点的配体受体。关于内西平，特别是非肽内西平，在睡眠领域中的作用知之甚少，除了很少有报告称内西平昏迷中观察到高浓度，这是一种罕见的特发性复发性昏迷现象。我们重点研究了被认为具有内氮平功能的次黄嘌呤和血栓素 A2。本研究旨在检查 24 小时急性睡眠剥夺对没有睡眠问题或障碍的健康受试者血液中次黄嘌呤和血栓素 A2 水平的影响。结果显示，与不受限制的正常睡眠条件相比，睡眠剥夺后的早晨两种化合物显着减少，从而表明这些内西平在睡眠时有规律地分泌，因此是睡眠过程所必需的。