Sleep/Wake Behaviors in Mice During Pregnancy and Pregnancy-Associated Hypertensive Mice

Sleep/Wake Behaviors in Mice During Pregnancy and Pregnancy-Associated Hypertensive Mice
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DOI:
10.1093/sleep/zsx209
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发表时间:
2018-03-01
期刊:
影响因子:
5.6
通讯作者:
Yanagisawa, Masashi
Yanagisawa, Masashi
中科院分区:
医学2区
文献类型:
--
作者:
Komiya, Haruna;Miyoshi, Chika;Yanagisawa, Masashi

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研究目标:人类和其他哺乳动物的睡眠在怀孕期间会发生变化。然而,尚未对小鼠怀孕期间的睡眠/觉醒进行研究。在这项研究中,我们检查了雌性 C57BL/6 小鼠在怀孕期间的睡眠/觉醒情况。我们还检查了先兆子痫、妊娠相关高血压 (PAH) 小鼠的睡眠/觉醒行为,其中血管紧张素增加会导致高血压。方法:根据妊娠前、妊娠期间和妊娠后的脑电图 (EEG) 或肌电图记录,检查雌性 C57BL/6 和 PAH 小鼠的睡眠/觉醒行为。为了检查高血压是否会破坏 PAH 小鼠血脑屏障的完整性,静脉注射伊文思蓝染料。还对给予血管紧张素 II 受体阻滞剂(奥美沙坦)的 PAH 小鼠和雌性筑波高血压小鼠进行了检查。结果:C57BL/6 小鼠在妊娠后期表现出总觉醒时间减少和非快速眼动 (NREM) 睡眠时间增加。快速眼动 (REM) 睡眠时间在怀孕期间没有变化。 PAH 小鼠在怀孕后期表现出脑电图普遍减慢,随后在分娩后恢复到明显正常的睡眠/觉醒状态。所有 PAH 小鼠的大脑中均表现出伊文思蓝染料的多处局灶性渗漏。在 50% 的 PAH 小鼠中观察到棘波放电。给予奥美沙坦的 PAH 小鼠没有表现出脑电图普遍减慢。筑波高血压小鼠的清醒时间和非快速眼动睡眠时间正常,而总快速眼动睡眠时间减少。结论:这项研究显示了 C57BL/6 小鼠妊娠阶段特定的睡眠/觉醒变化。此外,PAH 小鼠可用作子痫的动物模型。
Study Objectives: In humans and other mammals, sleep is altered during pregnancy. However, no studies have been conducted on sleep/wakefulness during pregnancy in mice. In this study, we examined sleep/wakefulness in female C57BL/6 mice during pregnancy. We also examined sleep/wake behaviors in an animal model of preeclampsia, pregnancy-associated hypertensive (PAH) mice, in which increased angiotensin causes hypertension.Methods: Sleep/wake behaviors of female C57BL/6 and PAH mice were examined based on electroencephalogram (EEG) or electromyogram recordings before, during, and after pregnancy. To examine whether high blood pressure disrupts the integrity of the blood-brain barrier in PAH mice, Evans blue dye was injected intravenously. Angiotensin II receptor blocker (olmesartan)administered PAH mice and female Tsukuba hypertensive mice were also examined.Results: C57BL/6 mice showed a decreased total wake time and increased nonrapid eye movement (NREM) sleep time during late pregnancy. Rapid eye movement (REM) sleep time did not change during the course of pregnancy. PAH mice exhibited a general slowing of EEG during late pregnancy and subsequently returned to apparently normal sleep/wakefulness after delivery. All PAH mice exhibited multiple focal leakages of Evans blue dye in the brain. Spike-and-wave discharges were observed in 50% of PAH mice. Olmesartan-administered PAH mice did not show general slowing of EEG. Tsukuba hypertensive mice showed a normal time spent in wakefulness and NREM sleep and a decreased total REM sleep time.Conclusions: This study showed pregnant-stage-specific changes in sleep/wakefulness in C57BL/6 mice. Furthermore, PAH mice may be useful as an animal model for eclampsia.