Convergence of circadian and sleep regulatory mechanisms on hypocretin-1
Convergence of circadian and sleep regulatory mechanisms on hypocretin-1
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DOI：
10.1016/j.neuroscience.2004.07.049
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Meijer, JH
中科院分区：
文献类型：
--
作者：
Deboer, T;Overeem, S;Meijer, JH
下丘脑泌素是睡眠和清醒的潜在调节剂，其水平随着动物活动期间的昼夜循环而波动。每天的波动是由内部驱动的还是由外部光周期驱动的尚不清楚。我们研究了在没有环境光周期的情况下，竹红菌素的昼夜节律和动态平衡调节。为此，我们通过在枕大池植入微导管重复采集大鼠的脑脊液，并用放射免疫法测定了下丘脑-1的水平。这些实验也在接受视交叉上核(SCN)损伤的大鼠身上进行，视交叉上核是哺乳动物昼夜节律的主要起搏器。结果表明，对照组动物在恒定暗淡的红光下，下丘脑组织中存在持续的节律性。SCN损伤的动物没有表现出下丘脑的昼夜节律，平均下丘脑的水平非常低。结果表明，SCN对下丘脑肌素的节律性是必不可少的，并在动物的活动期诱导下丘脑肌红素水平的每天增加。此外，还进行了睡眠剥夺实验，以研究下丘脑肌素对体内平衡的调节。在对照组和SCN组动物中，睡眠剥夺导致下丘脑肌素水平升高，这表明下丘脑肌素的睡眠稳态控制独立于SCN发生。我们的数据表明，SCN的昼夜节律起搏器和睡眠稳态机制汇聚在一种单一的睡眠调节物质上。(C)2004年IBRO。爱思唯尔有限公司出版。保留所有权利。
Hypocretin is a potential regulator of sleep and wakefulness and its levels fluctuate with the day-night cycle with high levels during the animal's activity period. Whether the daily fluctuations are driven endogenously or by external light cycles is unknown. We investigated the circadian and homeostatic regulation of hypocretin in the absence of environmental light cycles. To this purpose we performed repetitive samplings of cerebrospinal fluid in rats through implanted microcannulas in the cisterna magna and determined hypocretin-1 levels by radioimmunoassay. These experiments were also performed in rats that received a lesion of the suprachiasmatic nucleus (SCN), a major pacemaker for circadian rhythms in mammals. The results showed sustained rhythmicity of hypocretin in constant dim red light in control animals. SCN-lesioned animals showed no circadian rhythms in hypocretin and mean hypocretin levels were remarkably low. The results indicate that the SCN is indispensable for rhythmicity in hypocretin and induces a daily increase in hypocretin levels during the animal's active phase. Additional sleep deprivation experiments were carried out to investigate homeostatic regulation of hypocretin. Hypocretin levels increased in response to sleep deprivation in both control and SCN-lesioned animals, demonstrating that sleep homeostatic control of hypocretin occurs independently from the SCN. Our data indicate that the circadian pacemaker of the SCN and sleep homeostatic mechanisms converge on one single sleep regulatory substance. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.