Fluctuation of extracellular hypocretin-1 (orexin A) levels in the rat in relation to the light-dark cycle and sleep-wake activities
Fluctuation of extracellular hypocretin-1 (orexin A) levels in the rat in relation to the light-dark cycle and sleep-wake activities
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DOI：
10.1046/j.0953-816x.2001.01725.x
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发表时间：
2001-10-01
影响因子：
3.4
通讯作者：
Nishino, S
中科院分区：
文献类型：
--
作者：
Yoshida, Y;Fujiki, N;Nishino, S
下丘脑泌素/食欲素是与睡眠调节和睡眠障碍发作性睡病有关的神经肽。为了研究下丘脑泌素活性如何在24小时内波动相对于睡眠-觉醒周期，我们测量了细胞外下丘脑泌素-1水平的变化，在外侧下丘脑和内侧丘脑的自由移动大鼠同步睡眠记录。下丘脑泌素水平表现出强烈的昼夜波动;水平缓慢增加，在黑暗期间（活跃期），并在光照期间（休息期）下降。水平与每个时期的清醒或睡眠量无关。虽然急性4小时光移没有改变下丘脑泌素水平，6小时的睡眠剥夺显着增加下丘脑泌素释放在强迫觉醒期间。因此，下丘脑泌素的活性可能在清醒时增加，并随着睡眠的发生而下降。这些发现，再加上白天难以保持清醒是下丘脑泌素缺乏型嗜睡症的主要症状之一，表明下丘脑泌素活性可能在长时间清醒期间对抗睡眠倾向方面至关重要。
Hypocretins/orexins are neuropeptides implicated in sleep regulation and the sleep disorder narcolepsy. In order to examine how hypocretin activity fluctuates across 24 h with respect to the sleep-wake cycle, we measured changes in extracellular hypocretin-1 levels in the lateral hypothalamus and medial thalamus of freely moving rats with simultaneous sleep recordings. Hypocretin levels exhibited a robust diurnal fluctuation; levels slowly increased during the dark period (active phase), and decreased during the light period (rest phase). Levels were not correlated with the amount of wake or sleep in each period. Although an acute 4-h light-shift did not alter hypocretin levels, 6-h sleep deprivation significantly increased hypocretin release during the forced-wake period. Hypocretin activity is, thus, likely to build up during wakefulness and decline with the occurrence of sleep. These findings, together with the fact that a difficulty in maintaining wakefulness during the daytime is one of the primary symptoms of hypocretin-deficient narcolepsy, suggest that hypocretin activity may be critical in opposing sleep propensity during periods of prolonged wakefulness.