Essential roles of GABA transporter-1 in controlling rapid eye movement sleep and in increased slow wave activity after sleep deprivation.
Essential roles of GABA transporter-1 in controlling rapid eye movement sleep and in increased slow wave activity after sleep deprivation.
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GABA 转运蛋白 1 在控制快速眼动睡眠和睡眠剥夺后慢波活动增加中的重要作用
DOI：
10.1371/journal.pone.0075823
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Huang ZL
中科院分区：
文献类型：
--
作者：
Xu XH;Qu WM;Bian MJ;Huang F;Fei J;Urade Y;Huang ZL
GABA是哺乳动物中枢神经系统中主要的抑制性神经递质，与睡眠调节密切相关。GABA转运蛋白亚型1 （GAT1）构建GABA高亲和力再摄取位点，调控GABA能在脑内的传递。然而，GAT1在睡眠-觉醒调节中的作用仍然难以捉摸。在目前的研究中，我们描述了GAT1敲除（KO）小鼠的自发睡眠-觉醒周期和对睡眠剥夺的反应。GAT1 KO小鼠在所有警觉性阶段均表现出占优势的theta-activity和显著的低频EEG功率降低。在基线条件下，KO小鼠的自发快速眼动（REM）睡眠在光照期和黑暗期均增加，非快速眼动（NREM）睡眠仅在光照期减少。KO小鼠从NREM睡眠到REM睡眠、从REM睡眠到清醒的状态转换也比WT小鼠多，REM和NREM睡眠次数也比WT小鼠多。在黑暗期，KO小鼠仅表现出更多的快速眼动睡眠。6小时的睡眠剥夺导致两种基因型的非快速眼动和快速眼动睡眠的反弹增加。然而，与它们各自的基线相比，WT小鼠的NREM睡眠的慢波活动强度部分短暂升高，而KO小鼠则完全保持不变。这些结果表明，GAT1在快速眼动睡眠和非快速眼动睡眠的调节中起着至关重要的作用。
GABA is the major inhibitory neurotransmitter in the mammalian central nervous system that has been strongly implicated in the regulation of sleep. GABA transporter subtype 1 (GAT1) constructs high affinity reuptake sites for GABA and regulates GABAergic transmission in the brain. However, the role of GAT1 in sleep-wake regulation remains elusive. In the current study, we characterized the spontaneous sleep-wake cycle and responses to sleep deprivation in GAT1 knock-out (KO) mice. GAT1 KO mice exhibited dominant theta-activity and a remarkable reduction of EEG power in low frequencies across all vigilance stages. Under baseline conditions, spontaneous rapid eye movement (REM) sleep of KO mice was elevated both during the light and dark periods, and non-REM (NREM) sleep was reduced during the light period only. KO mice also showed more state transitions from NREM to REM sleep and from REM sleep to wakefulness, as well as more number of REM and NREM sleep bouts than WT mice. During the dark period, KO mice exhibited more REM sleep bouts only. Six hours of sleep deprivation induced rebound increases in NREM and REM sleep in both genotypes. However, slow wave activity, the intensity component of NREM sleep was briefly elevated in WT mice but remained completely unchanged in KO mice, compared with their respective baselines. These results indicate that GAT1 plays a critical role in the regulation of REM sleep and homeostasis of NREM sleep.
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影响因子：
56.9
作者：
GUASTELLA, J;NELSON, N;KANNER, BI
通讯作者：
KANNER, BI
影响因子：
25
作者：
Huang, ZL;Qu, WM;Hayaishi, O
通讯作者：
Hayaishi, O
影响因子：
5.3
作者：
Chiu, CS;Brickley, S;Lester, HA
通讯作者：
Lester, HA
影响因子：
4.2
作者：
Cai, You-Qing;Cai, Guo-Qiang;Fei, Jian
通讯作者：
Fei, Jian
组胺 H1 受体敲除小鼠的睡眠-觉醒特征发生改变，且对 H3 受体拮抗剂缺乏唤醒反应。
DOI：
10.1073/pnas.0600451103
发表时间：
2006-03-21
影响因子：
11.1
作者：
Huang, ZL;Mochizuki, T;Hayaishi, O
通讯作者：
Hayaishi, O