Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.
Psychoneuroendocrinology. 2010 Jun;35(5):775-84. doi: 10.1016/j.psyneuen.2009.11.004. Epub 2009 Dec 4.
Epidemiological and experimental studies suggest a high prevalence of cognitive impairment and social behavior deficits in adolescents and adults that have experienced prenatal exposure to adverse conditions. This study investigated whether sleep deprivation during the pre-implantation stage of development alters the physiological, behavioral and oxidative metabolic processes in adult male mouse offspring. One group of dams was continuously sleep-deprived using the platform technique from gestational days 0 to 3 (PSD 72). Three additional groups were sleep-deprived by gentle handling for 6h on gestational days 1 (GH 1), 2 (GH 2) or 3 (GH 3). After sleep deprivation, homocysteine, cysteine, corticosterone, estrogen and progesterone concentrations were measured from the experimental mothers and time-matched controls. The sizes and weights of the male pups were measured at various stages throughout the experiment. At PND 90, behavioral (Activity Box and Elevated Plus Maze) and biochemical parameters were assessed. The dams' plasma progesterone concentrations decreased in the PSD 72 group, and the levels of plasma estradiol increased in GH 2. Corticosterone levels were found to increase after all sleep-deprivation procedures. Homocysteine concentrations increased in the GH 2 but decreased in the PSD 72 group. The offspring of GH 1 mothers exhibited decreased superoxide dismutase activity. Exposure to sleep deprivation had a long-lasting impact on tissue weight; in particular, there was a decrease in hemilateral epididymal fat weight in mature animals from the PSD 72 group. Although some of the alterations observed in the mothers (elevated estrogen and corticosterone levels and decreased progesterone) might have played a role in the permanent alterations in the adult offspring, they were not the main cause. The homocysteine changes detected in the sleep-deprived dams may contribute to redox changes, controlling gene expression and shaping epigenetic development.
流行病学和实验研究表明，经历过产前暴露于不利条件的青少年和成年人认知障碍和社会行为缺陷的发生率很高。本研究调查了胚胎植入前发育阶段的睡眠剥夺是否会改变成年雄性小鼠后代的生理、行为和氧化代谢过程。一组孕鼠从妊娠第 0 天到第 3 天（PSD72）连续使用平台技术进行睡眠剥夺。另外三组孕鼠在妊娠第 1 天（GH1）、第 2 天（GH2）或第 3 天（GH3）进行 6 小时的轻度处理。睡眠剥夺后，从实验母鼠和时间匹配的对照组中测量同型半胱氨酸、半胱氨酸、皮质酮、雌激素和孕酮的浓度。在整个实验过程中，不同阶段测量雄性幼鼠的大小和体重。在 PND90 时，评估行为（活动箱和高架十字迷宫）和生化参数。PSD72 组母鼠血浆孕酮浓度降低，GH2 组血浆雌二醇水平升高。所有睡眠剥夺程序后皮质酮水平升高。GH2 组同型半胱氨酸浓度升高，PSD72 组降低。GH1 组母鼠的后代超氧化物歧化酶活性降低。暴露于睡眠剥夺对组织重量有持久影响；特别是，PSD72 组成熟动物的单侧附睾脂肪重量减少。尽管母亲观察到的一些变化（雌激素和皮质酮水平升高，孕酮水平降低）可能在成年后代的永久性变化中发挥了作用，但它们不是主要原因。睡眠剥夺母鼠中检测到的同型半胱氨酸变化可能导致氧化还原变化，控制基因表达并塑造表观遗传发育。
