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缺乏1型大麻素受体的小鼠存在多种睡眠改变。

Multiple sleep alterations in mice lacking cannabinoid type 1 receptors.

作者信息

Silvani Alessandro, Berteotti Chiara, Bastianini Stefano, Lo Martire Viviana, Mazza Roberta, Pagotto Uberto, Quarta Carmelo, Zoccoli Giovanna

机构信息

PRISM lab, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.

Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, S. Orsola University Hospital, Alma Mater Studiorum - University of Bologna, Bologna, Italy.

出版信息

PLoS One. 2014 Feb 20;9(2):e89432. doi: 10.1371/journal.pone.0089432. eCollection 2014.

Abstract

Cannabinoid type 1 (CB1) receptors are highly expressed in the brain and play a role in behavior control. Endogenous cannabinoid signaling is modulated by high-fat diet (HFD). We investigated the consequences of congenital lack of CB1 receptors on sleep in mice fed standard diet (SD) and HFD. CB1 cannabinoid receptor knock-out (KO) and wild-type (WT) mice were fed SD or HFD for 4 months (n = 9-10 per group). Mice were instrumented with electroencephalographic (EEG) and electromyographic electrodes. Recordings were performed during baseline (48 hours), sleep deprivation (gentle handling, 6 hours), sleep recovery (18 hours), and after cage switch (insomnia model paradigm, 6 hours). We found multiple significant effects of genotype on sleep. In particular, KO spent more time awake and less time in non-rapid-eye-movement sleep (NREMS) and rapid-eye-movement sleep (REMS) than WT during the dark (active) period but not during the light (rest) period, enhancing the day-night variation of wake-sleep amounts. KO had slower EEG theta rhythm during REMS. REMS homeostasis after sleep deprivation was less effective in KO than in WT. Finally, KO habituated more rapidly to the arousing effect of the cage-switch test than WT. We did not find any significant effects of diet or of diet x genotype interaction on sleep. The occurrence of multiple sleep alterations in KO indicates important roles of CB1 cannabinoid receptors in limiting arousal during the active period of the day, in sleep regulation, and in sleep EEG in mice.

摘要

1型大麻素(CB1)受体在大脑中高度表达,并在行为控制中发挥作用。内源性大麻素信号传导受高脂饮食(HFD)调节。我们研究了先天性缺乏CB1受体对喂食标准饮食(SD)和HFD的小鼠睡眠的影响。将CB1大麻素受体敲除(KO)小鼠和野生型(WT)小鼠喂食SD或HFD 4个月(每组n = 9 - 10)。给小鼠植入脑电图(EEG)和肌电图电极。在基线期(48小时)、睡眠剥夺期(轻柔处理,6小时)、睡眠恢复期(18小时)以及笼子转换后(失眠模型范式,6小时)进行记录。我们发现基因型对睡眠有多种显著影响。特别是,在黑暗(活动)期,KO小鼠比WT小鼠清醒时间更长,非快速眼动睡眠(NREMS)和快速眼动睡眠(REMS)时间更短,但在光照(休息)期则不然,这增强了昼夜觉醒 - 睡眠量的变化。KO小鼠在REMS期间的EEG θ节律较慢。睡眠剥夺后的REMS稳态在KO小鼠中比WT小鼠更无效。最后,KO小鼠比WT小鼠更快地适应笼子转换测试的唤醒效应。我们未发现饮食或饮食×基因型相互作用对睡眠有任何显著影响。KO小鼠中出现的多种睡眠改变表明CB1大麻素受体在限制白天活动期的觉醒、睡眠调节以及小鼠睡眠EEG方面发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ba9/3930731/d14115d7b246/pone.0089432.g001.jpg

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