Adenosine: A mediator of the sleep-inducing effects of prolonged wakefulness
Adenosine: A mediator of the sleep-inducing effects of prolonged wakefulness
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DOI：
10.1126/science.276.5316.1265
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发表时间：
1997-05-23
期刊：
影响因子：
56.9
通讯作者：
McCarley, RW
中科院分区：
文献类型：
--
作者：
Porkka-Heiskanen, T;Strecker, RE;McCarley, RW
主观的和脑电图的唤醒都随着先前清醒的持续时间而减少。这里报道的数据表明，主要标准的神经睡眠因子介导的睡眠的影响，长时间的觉醒是满意的腺苷，神经调质的细胞外浓度增加与脑代谢，在体外，抑制基底前脑胆碱能神经元。在自由行为的猫在体内微透析测量表明，基底前脑胆碱能区的腺苷细胞外浓度增加，在自发觉醒与慢波睡眠相比，表现出持续的，长时间的觉醒过程中进行性增加，并在恢复睡眠缓慢下降。此外，长时间觉醒后发生的睡眠-觉醒曲线被模拟增加细胞外腺苷诱导的胆碱能基底前脑中的腺苷转运抑制剂的微透析灌注，但不是通过在控制非胆碱能区域灌注。
Both subjective and electroencephalographic arousal diminish as a function of the duration of prior wakefulness. Data reported here suggest that the major criteria for a neural sleep factor mediating the somnogenic effects of prolonged wakefulness are satisfied by adenosine, a neuromodulator whose extracellular concentration increases with brain metabolism and which, in vitro, inhibits basal forebrain cholinergic neurons. In vivo microdialysis measurements in freely behaving cats showed that adenosine extracellular concentrations in the basal forebrain cholinergic region increased during spontaneous wakefulness as contrasted with slow wave sleep; exhibited progressive increases during sustained, prolonged wakefulness; and declined slowly during recovery sleep. Furthermore, the sleep-wakefulness profile occurring after prolonged wakefulness was mimicked by increased extracellular adenosine induced by microdialysis perfusion of an adenosine transport inhibitor in the cholinergic basal forebrain but not by perfusion in a control noncholinergic region.