Department of Pharmacodynamics, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, Hungary.
Neurochem Int. 2011 Oct;59(5):686-94. doi: 10.1016/j.neuint.2011.06.015. Epub 2011 Jun 28.
Rapid eye movement (REM) sleep rebound following REM deprivation using the platform-on-water method is characterized by increased time spent in REM sleep and activation of melanin-concentrating hormone (MCH) expressing neurons. Orexinergic neurons discharge reciprocally to MCH-ergic neurons across the sleep-wake cycle. However, the relation between REM architecture and the aforementioned neuropeptides remained unclear. MCH-ergic neurons can be divided into two subpopulations regarding their cocaine- and amphetamine-regulated transcript (CART) immunoreactivity, and among them the activation of CART-immunoreactive subpopulation is higher during the REM rebound. However, the possible role of stress in this association has not been elucidated. Our aims were to analyze the relationship between the architecture of REM rebound and the activation of hypothalamic MCH-ergic and orexinergic neurons. We also intended to separate the effect of stress and REM deprivation on the subsequent activation of subpopulations of MCH-ergic neurons. In order to detect neuronal activity, we performed MCH/cFos and orexin/cFos double immunohistochemistry on home cage, sleep deprived and sleep-rebound rats using the platform-on-water method with small and large (stress control) platforms. Furthermore, REM architecture was analyzed and a triple MCH/CART/cFos immunohistochemistry was also performed on the rebound groups in the same animals. We found that the activity of MCH- and orexin-immunoreactive neurons during REM rebound was positively and negatively correlated with the number of REM bouts, respectively. A negative reciprocal correlation was also found between the activation of MCH- and orexin-immunoreactive neurons during REM rebound. Furthermore, difference between the activation of CART-immunoreactive (CART-IR) and non-CART-immunoreactive MCH-ergic neuron subpopulations was found only after selective REM deprivation, it was absent in the large platform (stress control) rebound group. These results support the role of CART-IR subpopulation of MCH-ergic neurons and the inverse relationship of MCH and orexin in the regulation of REM sleep after REM sleep deprivation.
快速眼动 (REM) 睡眠剥夺后使用水上平台法（platform-on-water method）产生的 REM 睡眠反弹的特征是 REM 睡眠时间增加和黑色素浓缩激素 (MCH) 表达神经元的激活。在整个睡眠-觉醒周期中，食欲素能神经元与 MCH 能神经元呈反向放电。然而，REM 结构与上述神经肽之间的关系尚不清楚。根据可卡因和安非他命调节转录物 (CART) 的免疫反应，MCH 能神经元可分为两个亚群，其中 CART-免疫反应亚群在 REM 反弹期间的激活更高。然而，这种关联中应激的可能作用尚未阐明。我们的目的是分析 REM 反弹的结构与下丘脑 MCH 能和食欲素能神经元的激活之间的关系。我们还打算分离应激和 REM 剥夺对随后 MCH 能神经元亚群激活的影响。为了检测神经元活动，我们使用水上平台法（platform-on-water method）和小平台（stress control）和大平台（small and large）对 home cage、睡眠剥夺和睡眠反弹大鼠进行了 MCH/cFos 和 orexin/cFos 双重免疫组织化学检测。此外，我们还在同一动物的反弹组中进行了 REM 结构分析和三重 MCH/CART/cFos 免疫组织化学检测。我们发现，在 REM 反弹期间，MCH 和食欲素免疫反应性神经元的活性与 REM 发作的数量呈正相关和负相关。在 REM 反弹期间，MCH 和食欲素免疫反应性神经元的激活也呈负相关。此外，只有在选择性 REM 剥夺后才发现 CART-免疫反应性（CART-IR）和非 CART-免疫反应性 MCH 能神经元亚群之间的激活差异，而在大平台（stress control）反弹组中则不存在。这些结果支持了 CART-IR 亚群的 MCH 能神经元和 MCH 与食欲素在 REM 睡眠剥夺后调节 REM 睡眠中的作用和反向关系。
