Haruna Komiya1,2, Chika Miyoshi1, Kanako Iwasaki1, Noriko Hotta-Hirashima1, Aya Ikkyu1, Satomi Kanno1, Takato Honda1, Masahiko Gosho3, Hiromi Hamada2, Toyomi Satoh2, Akiyoshi Fukamizu4, Hiromasa Funato1,5, Masashi Yanagisawa1,4,5,6. 1. International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan. 2. Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 3. Department of Biostatistics, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 4. Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, Japan. 5. Department of Anatomy, Faculty of Medicine, Toho University, Ota-ku, Tokyo, Japan. 6. Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX.
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.
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 PAHmice 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 PAHmice, Evans blue dye was injected intravenously. Angiotensin II receptor blocker (olmesartan)-administered PAHmice and female Tsukuba hypertensivemice 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. PAHmice exhibited a general slowing of EEG during late pregnancy and subsequently returned to apparently normal sleep/wakefulness after delivery. All PAHmice exhibited multiple focal leakages of Evans blue dye in the brain. Spike-and-wave discharges were observed in 50% of PAHmice. Olmesartan-administered PAHmice did not show general slowing of EEG. Tsukuba hypertensivemice 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, PAHmice may be useful as an animal model for eclampsia.
Authors: Thomas Topilko; Silvina L Diaz; Catarina M Pacheco; Florine Verny; Charly V Rousseau; Christoph Kirst; Charlotte Deleuze; Patricia Gaspar; Nicolas Renier Journal: Neuron Date: 2022-02-04 Impact factor: 18.688