Santangeli Olena, Lehtikuja Henna, Palomäki Eeva, Wigren Henna-Kaisa, Paunio Tiina, Porkka-Heiskanen Tarja
Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Department of Psychiatry, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Sleep. 2016 Dec 1;39(12):2211-2221. doi: 10.5665/sleep.6328.
Adverse early-life events induce behavioral psychopathologies and sleep changes in adulthood. In order to understand the molecular level mechanisms by which the maltreatment modifies sleep, valid animal models are needed. Changing pups between mothers at early age (cross-fostering) may satisfyingly model adverse events in human childhood.
Cross-fostering (CF) was used to model mild early-life stress in male and female Wistar rats. Behavior and gene expression in the basal forebrain (BF), cortex, and hypothalamus were assessed during adolescence and adulthood. Spontaneous sleep, sleep homeostasis, and BF extracellular adenosine levels were assessed in adulthood.
CF rats demonstrated increased number of REM sleep onsets in light and dark periods of the day. Total REM and NREM sleep duration was also increased during the light period. While sleep homeostasis was not severely affected, basal level of adenosine in the BF of both male and female CF rats was lower than in controls. CF did not lead to considerable changes in behavior.
Even when the consequences of adverse early-life events are not observed in tests for anxiety and depression, they leave a molecular mark in the brain, which can act as a vulnerability factor for psychopathologies in later life. Sleep is a sensitive indicator for even mild early-life stress.
早期生活中的不良事件会导致成年期出现行为心理病理学和睡眠变化。为了了解虐待改变睡眠的分子水平机制,需要有效的动物模型。在幼年时更换幼崽的母亲(交叉寄养)可以很好地模拟人类童年时期的不良事件。
采用交叉寄养(CF)对雄性和雌性Wistar大鼠的早期轻度生活压力进行建模。在青春期和成年期评估基底前脑(BF)、皮层和下丘脑的行为和基因表达。在成年期评估自发睡眠、睡眠稳态和BF细胞外腺苷水平。
CF大鼠在白天的明期和暗期快速眼动睡眠起始次数增加。明期的总快速眼动和非快速眼动睡眠时间也增加。虽然睡眠稳态没有受到严重影响,但雄性和雌性CF大鼠BF中的腺苷基础水平低于对照组。CF没有导致行为上的显著变化。
即使在焦虑和抑郁测试中未观察到早期生活不良事件的后果,它们也会在大脑中留下分子印记,这可能成为后期生活中心理病理学的一个易感性因素。睡眠是即使是轻度早期生活压力的敏感指标。