Disrupted sleep-wake regulation in type 1 equilibrative nucleoside transporter knockout mice.
Disrupted sleep-wake regulation in type 1 equilibrative nucleoside transporter knockout mice.
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DOI：
10.1016/j.neuroscience.2015.06.037
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发表时间：
2015-09-10
期刊：
影响因子：
3.3
通讯作者：
Basheer R
中科院分区：
文献类型：
--
作者：
Kim T;Ramesh V;Dworak M;Choi DS;McCarley RW;Kalinchuk AV;Basheer R
1型平衡型核苷转运蛋白（ENT 1）参与调节细胞外腺苷（[AD]ex）的水平。在基底前脑（BF）中，[AD]ex水平在清醒期间增加，并且与随后的非快速眼动睡眠（NREMS）期间脑电图（EEG）δ（0.75-4.5Hz）活动（NRδ）的增加密切对应。因此，在BF中，[AD]ex充当睡眠稳态的生化标志物。θ范围（5- 9 Hz，Wθ）的清醒EEG活动也被描述为睡眠稳态的标志。Wθ和NRδ之间的逐小时时间关系尚不清楚。在这项研究中，我们研究了在自发睡眠觉醒和睡眠剥夺（SD）和恢复睡眠的ENT 1基因敲除（KO）小鼠的睡眠稳态的这些脑电图标记之间的关系。我们观察到，与野生型（WT）同窝小鼠相比，ENT 1 KO小鼠在光照期的基线NREMS量减少，伴随着每小时的Wθ与随后一小时的NRδ之间的弱相关性。低剂量腺苷灌流BF不仅加强了Wθ -NRδ关系，而且增加了NREMS，使之与WT同窝小鼠相匹配，表明ENT 1 KO小鼠[AD]ex降低。然而，在ENT 1 KO小鼠中，SD诱导的BF中的[AD]ex增加和睡眠稳态的EEG标志物之间的线性相关性不受影响，这表明在SD期间，ENT 1以外的来源有助于[AD]ex增加。我们的数据提供了证据的差异调节觉醒相关的[AD]ex在自发与延长觉醒。
The type 1 equilibrative nucleoside transporter (ENT1) is implicated in regulating the levels of extracellular adenosine ([AD]ex ). In the basal forebrain (BF) the levels of [AD]ex increase during wakefulness and closely correspond to the increases in the electroencephalogram (EEG) delta (0.75–4.5Hz) activity (NRδ) during subsequent non-rapid eye movement sleep (NREMS). Thus in the BF, [AD]ex serves as a biochemical marker of sleep homeostasis. Waking EEG activity in theta range (5–9Hz, Wθ) is also described as a marker of sleep homeostasis. An hour-by-hour temporal relationship between the Wθ and NRδ is unclear. In this study we examined the relationship between these EEG markers of sleep homeostasis during spontaneous sleep-wakefulness and during sleep deprivation (SD) and recovery sleep in the ENT1 gene knockout (KO) mouse. We observed that baseline NREMS amount was decreased during light period in ENT1 KO mice, accompanied by a weak correlation between Wθ of each hour and NRδ of its subsequent hour when compared to their wild-type (WT) littermates. Perfusion of low dose of adenosine into BF not only strengthened the Wθ –NRδ relationship, but also increased NREMS to match with the WT littermates suggesting decreased [AD]ex in ENT1 KO mice. However, the SD-induced [AD]ex increase in the BF and the linear correlation between the EEG markers of sleep homeostasis were unaffected in ENT1KO mice suggesting that during SD, sources other than ENT1 contribute to increase in [AD]ex. Our data provide evidence for a differential regulation of wakefulness-associated [AD]ex during spontaneous vs prolonged waking.