Department of Psychobiology-Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu, 862, 1st floor, São Paulo, SP, 04023062, Brazil.
Group of Psychosomatics, Universidade Ibirapuera, São Paulo, Brazil.
Mol Neurobiol. 2018 Apr;55(4):2884-2896. doi: 10.1007/s12035-017-0541-3. Epub 2017 Apr 28.
Adolescence is marked by major physiological changes, including those in the sleep-wake cycle, such as phase delay, which may result in reduced sleep hours. Sleep restriction and/or deprivation in adult rats activate stress response and seem to be a risk factor for triggering emotional disorders. In the present study, we sought to evaluate the behavioral and neurobiological consequences of prolonged REM sleep restriction in juvenile male rats. Immediately after weaning, on postnatal day 21, three males from each litter were submitted to REM sleep deprivation and the other three animals were maintained in their home-cages. REM sleep restriction (REMSR) was accomplished by placing the animals in the modified multiple platform method for 18 h and 6 h in the home-cage, where they could sleep freely; the sleep restriction lasted 21 consecutive days, during which all animals were measured and weighed every 3 days. After the end of this period, all animals were allowed to sleep freely for 2 days, and then the behavioral tests were performed for evaluation of depressive and anxiety-like profiles (sucrose negative contrast test and elevated plus maze, EPM). Blood sampling was performed 5 min before and 30 and 60 min after the EPM for determination of corticosterone plasma levels. The adrenals were weighed and brains collected and dissected for monoamine levels and receptor protein expression. REMSR impaired the physical development of adolescents, persisting for a further week. Animals submitted to REMSR exhibited higher basal corticosterone levels and a greater anxiety index in the EPM, characteristic of an anxious profile. These animals also exhibited higher noradrenaline levels in the amygdala and ventral hippocampus, without any change in the expression of β1-adrenergic receptors, as well as higher serotonin and reduced turnover in the dorsal hippocampus, with diminished expression of 5-HT1. Finally, greater concentration of BDNF was observed in the dorsal hippocampus in chronically sleep-restricted animals. Chronic REMSR during puberty impaired physical development and induced anxiety-like behavior, attributed to increased noradrenaline and serotonin levels in the amygdala and hippocampus.
青春期的特点是发生重大的生理变化，包括睡眠-觉醒周期的变化，如相位延迟，这可能导致睡眠时间减少。在成年大鼠中，睡眠限制和/或剥夺会激活应激反应，似乎是引发情绪障碍的一个危险因素。在本研究中，我们试图评估 REM 睡眠剥夺对青春期雄性大鼠的行为和神经生物学的影响。在断奶后，即出生后第 21 天，每个窝中的三只雄性幼鼠被置于 REM 睡眠剥夺组，另外三只幼鼠被置于其原笼中。通过将动物置于改良的多平台方法中 18 小时和在原笼中 6 小时来进行 REM 睡眠限制（REMSR），在原笼中它们可以自由睡眠；睡眠限制持续 21 天，在此期间，每 3 天对所有动物进行测量和称重。在此期间结束后，所有动物都被允许自由睡眠 2 天，然后进行行为测试，以评估抑郁和焦虑样表型（蔗糖阴性对比测试和高架十字迷宫，EPM）。在 EPM 之前和之后 5 分钟、30 分钟和 60 分钟进行采血，以测定皮质酮的血浆水平。测量肾上腺的重量，并收集大脑进行单胺水平和受体蛋白表达的测定。REMSR 损害了青少年的身体发育，持续了一周。与对照组相比，接受 REMSR 的动物基础皮质酮水平更高，在 EPM 中的焦虑指数更高，表现出焦虑样表型。这些动物的杏仁核和腹侧海马体中的去甲肾上腺素水平也更高，β1-肾上腺素能受体的表达没有变化，而背侧海马体中的 5-羟色胺水平更高，且周转率降低，5-HT1 的表达减少。最后，在慢性睡眠限制的动物中，观察到背侧海马体中 BDNF 的浓度更高。青春期慢性 REMSR 损害了身体发育，并引起焦虑样行为，这归因于杏仁核和海马体中去甲肾上腺素和 5-羟色胺水平的增加。
