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

Abstract

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.