It will fall out within hours and dissolves in a days time. We could not evaluate the size of each leakage because of its vague boundary and multiple overlaps. The data from individual mice are presented as the group mean ± SEM. A general slowing of EEG in PAH mice during late pregnancy was confirmed by the high total δ density during late pregnancy compared with that during mid pregnancy (Figure 4A). (A) Power density during wake before, during, and after pregnancy in wild-type mice. EEG and EMG during pregnancy in wild-type and PAH mice. Gabriel Goh 26,679 views. The World Health Organization Multicounty Survey reported that preeclampsia and eclampsia develop in 2%–3% and 0.3% of pregnancies, respectively [24]. Before pregnancy, the daily total wake time of female mice was 868 ± 29.2 min, consistent with a previous report and much longer than that of male mice [38]. The present study also supports PAH mice as an animal model for eclampsia, based on seizures, altered sleep/wakefulness, fewer spontaneous activities, and high perinatal mortality. In summary, the present study revealed a similarity in the sleep changes during pregnancy between humans and mice [6, 7], which provides a basis for future studies on sleep regulation in animal models for human diseases during pregnancy. As eclampsia patients often exhibit hyperintensity on T2-weighted brain MRI indicative of vasogenic edema [28–31], acute severe hypertension in PAH mice may disrupt the blood–brain barrier (BBB) [32], but PAH mice have not been examined for the integrity of the BBB. Hi everyone! (A–C) Total time spent in wake (A), wake episode duration (B), and wake episode number (C) before, during, and after pregnancy in wild-type mice. Published by Oxford University Press on behalf of the Sleep Research Society. Like a typical human teenager, mice are undeniably nocturnal and voraciously hungry. EEG spectrogram was drawn using multitaper method [36] (time-half bandwidth 3, number of tapers 5, window size 30 s, overlap 0.5) implemented in the Chronux tool box [37] for MATLAB. Since there were many epochs that we could not properly classify into wake or NREMS during late pregnancy, we evaluated the sleep/wakefulness of PAH mice except for those in late pregnancy. The same is true of laboratory mice. Identify the sex of your hamster. Mice that showed multiple altered parameters in wakefulness, NREMS, and REMS during late pregnancy quickly returned to normal sleep/wakefulness, excluding the decreased episode duration of wakefulness and REMS. (D–F) Total time spent in NREM sleep (NREMS) (D), NREMS episode duration (E), and NREMS episode number (F) before, during early and mid-pregnancy, and postpartum in PAH mice. Haruna Komiya, MD, Chika Miyoshi, PhD, Kanako Iwasaki, BSc, Noriko Hotta-Hirashima, MS, Aya Ikkyu, MS, Satomi Kanno, Takato Honda, BSc, Masahiko Gosho, PhD, Hiromi Hamada, MD, PhD, Toyomi Satoh, MD, PhD, Akiyoshi Fukamizu, PhD, Hiromasa Funato, MD, PhD, Masashi Yanagisawa, MD, PhD, Sleep/Wake Behaviors in Mice During Pregnancy and Pregnancy-Associated Hypertensive Mice, Sleep, Volume 41, Issue 3, March 2018, zsx209, https://doi.org/10.1093/sleep/zsx209. They can stand on the hind legs, as well, and are supported by the tail, which also provides balance while in motion. (D) NREMS δ density before, during, and after pregnancy. The systolic blood pressure of PAH mice was 100–110 mm Hg which is similar to that of wild-type mice until pregnant day 12, started to increase at pregnant day 13, up to 160 mm Hg just prior to delivery. There was no difference in the wake episode duration (Figure 8B) or the wake episode number (Figure 8C). Does Investing in Low-income Urban Neighborhoods Improve Sleep? Four electrode pins were lowered to the dura under stereotaxic control, and two flexible wires for EMG recording were inserted in the neck muscles and subsequently attached to the skull using dental cement. Infanticide may be part of maternal behavior in the wild; under conditions when the successful rearing of a litter is unlikely this may be adaptive. Studies in the laboratory and under semi-natural conditions have shown that the pups benefit from such communal nursing in terms of increased growth and survival. The daily time spent in REMS of postpartum PAH mice was longer than that during early and mid pregnancy (F = 9.058, df = 3, p = .002; Figure 5G), likely reflecting a rebound phenomenon after the drastically reduced REMS time during late pregnancy (see below). Since the systolic blood pressure of THM is similar to that of olmesartan-administered PAH mice, the sleep/wake behaviors of these mice allow us to examine how mild-to-moderate hypertension affects sleep. And in this video, I’m gonna teach you some stuff about pregnant mice. This study also proposes that PAH mice may be an animal model of eclampsia. Although most behavioral studies have been conducted using male C57BL/6 mice, male-biased research results may hinder the characterization of sexually dimorphic effects, which may lead to an underestimation of risks for females [15]. Youssef AM, Hamidian Jahromi A, Vijay CG, Granger DN, Alexander JS. de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T. Saito T, Ishida J, Takimoto-Ohnishi Eet al. Like many pregnant women, Leigh Llemit didn't have appetite on her first 2 months of pregnancy, but turned into a voracious eater once past that stage. Hormonal changes underlie the first component to appear in the pregnant mouse female, nest building; however the sound of pups can also induce nest building in non-pregnant nulliparious (virgin) females. This was not an industry-supported study. The wake episode duration during the light phase during late pregnancy was shorter than that before and after pregnancy (F = 4.270, df = 4, p = .008; Figure 2B). Thank you for submitting a comment on this article. Olmesartan treatment also decreased the total δ density of PAH mice to that of nonpregnant PAH (human angiotensinogen–transgenic) mice (Figure 7B). The duration of the REMS episode decreased during mid and late pregnancy and postpartum compared with that before pregnancy (F = 13.474, df = 4, p < .0001; Figure 2H). A playful chase is usually also a quieter chase; mice in a squabble tend to be more vocal. However, behavior of the offspring was altered. It is important to mention first that the mother rat may not … For example, pregnant women are often more anxious about the possibility of bodily harm. Although various kinds of preeclampsia model mice, including PAH mice, have been reported, none of them fully reproduce human preeclampsia in terms of pathogenesis, symptoms, and responses to pharmacological intervention. (D–F) Total time spent in NREMS (D), NREMS episode duration (E), and NREMS episode number (F) before, during, and after pregnancy. The total REMS time of female THM was shorter than that of female wild-type mice (Figure 8G). Sleep/wake behaviors of female C57BL/6 and PAH mice were examined based on electroencephalogram (EEG) or electromyogram recordings before, during, and after pregnancy. Total REMS time was not significantly changed before, during, and after pregnancy (Figure 2G). In the present study, we evaluated sleep/wake behaviors during pregnancy in C57BL/6 mice by analyzing the electroencephalogram (EEG) or electromyogram (EMG), which provides a basis for future studies on the mechanism of sleep regulation during pregnancy. (G–I) Total time spent in REMS (G), REMS episode duration (H), and REMS episode number (I) before, during, and after pregnancy. Part II. Do they make noise? EEGs and sleep/wakefulness of olmesartan-administered PAH mice. (B and C) Representative EEG and EMG recordings showing the periodic spike-and-wave discharges of two PAH mice. the mouse strains produced are genetically well defi ned. The daily time spent in REMS and the daily number of REMS episodes were not altered during the course of pregnancy, which is consistent with previously reported for pregnant rats [40, 43]. At 8–12 weeks of age (19–23 g), female wild-type, THM, and PAH mice were anesthetized using isoflurane (3%–4% for induction and 1%–2% for maintenance). *p < .05, **p < .01, ***p < .001. An acute increase in arterial blood pressure by 80 mm Hg disrupts the BBB integrity in rats [60]. Rapid eye movement (REM) sleep time did not change during the course of pregnancy. Neuroimaging studies of eclampsia patients revealed posterior reversible encephalopathy syndrome, which refers to reversible vasogenic cerebral edema in the posterior region of the cerebral cortex accompanied by acute neuropsychiatric symptoms [28–31]. We observed no difference in the REMS episode duration (Figure 5H) or REMS episode number (Figure 5I). A doe giving birth should never be disturbed. Pregnant does will exhibit increased nesting behavior as the day of kindling approaches. For REMS, the power density at 4 and 5 Hz during late pregnancy was higher than that before pregnancy (F = 4.865, df = 4, p = .004 for 4 Hz; F = 10.561, df = 4, p < .0001 for 5 Hz; Figure 3C). Similarly, the most commonly observed EEG abnormality in human eclampsia is generalized or focal slowing of EEG [28, 58, 59], and this abnormal EEG normalizes after the release from hypertension [59]. The power density of PAH mice did not exhibit any significant difference during NREMS (Figure 6B). Endometrial Receptivity and Embryo Implantation in Carnivores-Commonalities and Differences with Other Mammalian Species. Studies have found that some mouse models of autism make fewer squeaks than controls do. Importantly, the sleep/wake behaviors of postpartum mice were similar to nonpregnant mice, despite lactation and increased prolactin and oxytocin. *p < .05. Mice are social and care better for their young when they are housed with friends. Bokil H, Andrews P, Kulkarni JE, Mehta S, Mitra PP. Aggressive behavior seems to be related to gestation in the female mouse. One-way ANOVA followed by Tukey’s test. Consistently, receptors for estrogen are abundant in the preoptic area, which is involved in sleep regulation [50]. To the best of our knowledge, the present study is the first report on sleep/wakefulness during the course of pregnancy in mice. There was no difference in the wake episode duration (Figure 5B) and wake episode number (Figure 5C). EEG signals were subjected to a fast Fourier transform analysis from 1 to 30 Hz with a 1-Hz bin using MATLAB (MathWorks)-based custom software. Each treatment was completed within 5 min. PAH mice may be a useful model for the development of therapeutic intervention for eclampsia. PAH mice exhibit elevated blood pressure with severe proteinuria during late pregnancy, which are diagnostic criteria for human preeclampsia [19, 20]; however, these animals have not been examined for neuropsychiatric phenotypes. Despite the broad use of mice for preclinical studies, to the best of our knowledge, there have been no studies on sleep/wakefulness during pregnancy in mice. This dosage of olmesartan decreases the systolic blood pressure of PAH mice to approximately 120 mm Hg [26, 27]. The EEG spectrum analysis of REMS showed pregnancy-induced changes at 6 and 7 Hz from the early stages of pregnancy, although the physiological significance of this finding is not clear. Manipulating the Mouse Embryo: A Laboratory Manual, 3rd ed. The data are presented as the mean ± SEM. Three out of six PAH mice showed periodic abnormal discharges on EEG signals during late pregnancy (Figure 4B, C, and D). Parry BL, Fernando Martínez L, Maurer EL, López AM, Sorenson D, Meliska CJ. Sleep/wake behaviors during the course of pregnancy in PAH mice, except for during late pregnancy. The sleep/wakefulness in each 20-s epoch was classified as nonrapid eye movement (NREM) sleep (NREMS), rapid eye movement (REM) sleep (REMS), or wakefulness using MatLab (MathWorks)-based semiautomated staging system followed by visual inspection. The wake episode duration before pregnancy was significantly longer than that during mid, late, and after pregnancy (F = 7.429, df = 4, p < .0001; Figure 2B). An increased total REMS during postpartum was observed during the light phase (F = 11.141, df = 3, p = .0008; Figure 5G), but not during the dark phase. The male if present, may also participate in caring for pups (Weber & Olsson, 2008). It is very common for the female mouse to have her smaller territory inside of the males larger territory. Indeed, modification of the Keap1-Nrf2 pathway, which functions as a defense system for oxidative stress, enhances placental angiogenesis and survival rates of PAH mice and their fetuses independently of high blood pressure [68]. The total REMS time of PAH mice was only 4.3 ± 1.9 min (mean ± SEM), but olmesartan-administered PAH mice showed a significantly longer REMS time (F = 17.230, df = 2, p < .0001, Figure 7C). Although women with preeclampsia have a 3.7-fold increased risk of death compared with pregnant women without preeclampsia, women with eclampsia have a 42-fold increase [24]. Back to Top ... in order to minimize mouse-to-mouse variations in phenotype, the genetic background of a colony should be as uniform as possible. In this study, we examined sleep/wakefulness in female C57BL/6 mice during pregnancy. Habits of Mice | Mice Behavior. However, postpartum mice showed significantly longer total wake time during the light phase than before pregnancy (F = 3.271, df = 4, p = .025; Figure 2A). The data are presented as the mean ± SEM. Mom and You. (B) δ-Densities of all epochs of nonpregnant PAH (normotensive) mice (n = 6), PAH mice (n = 6), and olmesartan-administered PAH mice (n = 5) during late pregnancy. International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. Pregnant Mouse Behavior? Typically, periodic spike-and-wave discharges that were clearly different from background EEG activity occurred during the NREMS-like state and accompanied phasic EMG activities with jerky body movements (video in Supplementary Material), which typically lasted 10–15 min and repeated 4–6 times during the 24-hr period. https://secureservercdn.net/198.71.233.5/712.919.myftpupload.com/wp-content/uploads/2016/06/maternal-video.mp4. n = 6. Paul KN, Dugovic C, Turek FW, Laposky AD. A dam uses olfactory cues in her milk and urine to establish a unique social identity for her litter. Since PAH mice did not raise newborn pups and ignored them, pups of PAH mice were killed by decapitation. Surprisingly, the prominent abnormalities in EEG and EMG of PAH mice quickly disappeared within 2 days from delivery (Figure 1C and D). I took her to the vet a couple of days ago and they said she looked healthy (that was when we found out she was pregnant.) To the best of our knowledge, however, there have been no published studies on sleep/wakefulness during pregnancy in mice. Brussé IA, Peters NC, Steegers EA, Duvekot JJ, Visser GH. C57BL/6 mice showed a decreased total wake time and increased nonrapid eye movement (NREM) sleep time during late pregnancy. How to Know if Platy Fish is Pregnant? Mean episode durations were determined by dividing the total time spent in each state by the number of episodes of that state. In contrast, the total wake time during the light phase was similar to that before and during pregnancy. Analyses were carried out using two-sided tests and a statistical significance level of 0.05. There was no significant difference in NREMS δ density before, during, and after pregnancy (Figure 3D). In humans and other mammals, sleep is altered during pregnancy. Since Evans blue leakages were generally very light without an apparent boundary, we counted the number of dye leakages from the brain surface, which provided more reliable and reproducible evaluations than on brain slices. Food and water were delivered ad libitum. The data from individual mice are presented as the group mean ± SEM. (A) δ-Densities of all epochs during mid, late, and after pregnancy. Increased angiotensin II causes acute and severe hypertension with proteinuria in PAH mice [9, 25], which can be alleviated by olmesartan, an angiotensin II receptor blocker, from 150–160 to 120 mm Hg in late pregnancy, which was still higher than that of normal pregnant mice, 100–110 mm Hg [26, 27]. Your comment will be reviewed and published at the journal's discretion. (D) NREMS δ density before, during early and mid pregnancy, and postpartum. Consistent with a previous report on high mortality [9], 3 out of 10 PAH mice died after delivery. In PAH mice, when a female angiotensinogen transgenic mouse conceives embryos carrying the human renin transgene, the pregnant mouse shows hypertension and proteinuria in late pregnancy because the human renin produced from the placenta processes human angiotensinogen into angiotensin I [9] and subsequently angiotensin II. That’s where the similarities between the lovable adolescent and the less-than-adorable house mouse end. Watch for nest-building behavior. For NREMS, power density at 4 Hz during late pregnancy was higher than that before pregnancy and during early pregnancy (F = 13.384, df = 4, p < .0001; Figure 3B). Maternal behavior is elicited through a combination of hormonal factors and external stimuli from the pups. The EEG spectrum of PAH mice in late pregnancy showed a decrease in high frequency power (>8 Hz) (Figure 1D), lacked a clear difference between the light and dark phases, and lacked any stretch of wake or sleep epochs (Figure 1D). Maternal interactions have implications in the physiological, psychological, and social development or mice and some of these effects remain into adulthood. Maternal behavior can be broken down into several categories such as: birth behavior, care of infants, suckling behavior, human interaction, and also negative maternal behavior. The total wake time of female THM was similar to that of female wild-type mice (Figure 8A). We also observed that half of the PAH mice showed spike-and-wave discharges during late pregnancy, based on EEG or EMG recording supplemented with video recording. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. Since PAH mice do not raise newborn pups and ignore them, we removed the newborn pups. She will also start to build a nest. Thus, a large-scale gene knockout program has been developed as a resource using C57BL/6 mice [13], and the subsequent phenomics program has continued to uncover the phenotypes of gene knockout mice [14]. The NREMS episode duration and episode number were similar before, early, mid, and after pregnancy (Figure 5E and F). By using optogenetic and pharmacogenetic approaches, the understanding of neural circuitries regulating sleep/wake behaviors has rapidly progressed [12]. After recording, the female mice were housed with a male mouse. Sleep/wakefulness was analyzed as previously described with some modifications [35]. To examine whether high blood pressure disrupts the integrity of the blood–brain barrier in PAH mice, Evans blue dye was injected intravenously. Search for other works by this author on: Department of Biostatistics, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan, Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, Japan, Department of Anatomy, Faculty of Medicine, Toho University, Ota-ku, Tokyo, Japan. The total NREMS time during the dark phase during late pregnancy was significantly longer than that before and during early pregnancy (F = 6.751, df = 4, p < .0001; Figure 2D). Interfering (adding unwanted scents from handling or removing scent by changing cages) with these olfactory identification cues risks disrupting maternal behavior, particularly during the first week following parturition. In addition to the physical effects of the growing uterus and embryos during pregnancy, hormonal changes may affect sleep/wake behaviors during pregnancy. Several scores of aggressive behavior rose progressively with the advance of gestation and reached a maximum toward the time of parturition. The present study showed that PAH mice exhibited markedly abnormal vigilance states with a generalized slowing of EEG during late pregnancy. REMS is characterized by θ (6–9 Hz)-dominant EEG and low amplitude of EMG. (C) Representative 8-s EEG and EMG during wake, NREMS, and REMS during mid and late pregnancy and postpartum in a PAH mouse. Unfortunately, if you got a pregnant mouse from the pet store she may be quite young and may not have the best mothering abilities. Oxford University Press is a department of the University of Oxford. Takahashi S, Fukamizu A, Hasegawa Tet al. (C) Power density during REMS before, during, and after pregnancy. For postpartum, we evaluated the third and fourth days after delivery because sleep/wake behaviors during the first 2 days after delivery varied widely depending on the time of delivery and the number of pups. Adopting 6 Mice (Vlog #5) - Duration: 6:59. If your cage has sawdust, dirt or other pliable material, watch to see if she uses it to build a nest for her young. Appropriate company for mice. Total time, episode duration, episode number, EEG power density, and δ density of wild-type and PAH mice were compared during the course of pregnancy using one-way repeated measures ANOVA (analysis of variance) followed by post hoc Tukey’s test. Within the male territory, there maybe just one female or many females with their own area. Changes in types of behaviour and how long mice spend doing particular behaviours can indicate that a mouse is in pain, or distress, or is suffering. In a cage devoid of any enrichment (a fancy term for mouse toys), many strains display unfavorable behavior, including barbering, reduced eating and reduced breeding. Total nonrapid eye movement sleep time was increased during the course of pregnancy. Despite the longer total NREMS time during late pregnancy, the NREMS episode duration during late pregnancy was shorter than that before and during early pregnancy (F = 5.168, df = 4, p = .003; Figure 2E). Thus, PAH mice exhibit a pathophysiologic mechanism similar to human eclampsia during late pregnancy. Some women appear to breeze through pregnancy with no problems at all. In addition, the administration of olmesartan alleviated sleep/wake behavior abnormalities of PAH mice during late pregnancy such as general slowing of EEG, loss of the circadian change in sleep/wakefulness, and a drastic reduction in REMS. Consistent with pregnancy-stage-specific hypertension, PAH mice showed frequent spontaneous locomotion for foraging and exploration and exhibited normal EEG and EMG signals during wakefulness, NREMS, and REMS in early and mid pregnancy (Figure 1C). Strain differences have been demonstrated in behavior such as nest building and nursing (Weber & Olsson, 2008). Consistently, angiotensin II type-1a receptor is required for the high blood pressure in PAH mice [57]. Eclampsia is a severe phase of preeclampsia with the occurrence of convulsions and/or disturbed consciousness [20, 23]. During the dark phase, the duration of the NREMS episode during late pregnancy was significantly shorter than that before and during early pregnancy (F = 3.456, df = 4, p = .020; Figure 2E). Approaching delivery, an increased physical load such as the weight of embryos, extended uterus, and increasing abdominal pressure, may necessitate more sleep and rest in pregnant mice. 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