Liu Xinhe, Petit Jean-Marie, Ezan Pascal, Gyger Joël, Magistretti Pierre, Giaume Christian
Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241, Institut National de la Santé et de la Recherche Médicale Unité 1050, 75231 Paris Cedex 05, France; University Pierre et Marie Curie, ED, N°158, 75005 Paris, France; MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, 75005 Paris, France.
Laboratory of Neuroenergetic and Cellular Dynamics, Brain Mind Institute, Life Science Faculty, EPFL, 1015 Lausanne, Switzerland; Centre de Neurosciences Psychiatriques, Centre Hospitalier Universitaire Vaudois (CHUV), Site de Cery, 1008 Prilly, Switzerland.
Neuropharmacology. 2013 Dec;75:533-8. doi: 10.1016/j.neuropharm.2013.04.019. Epub 2013 May 9.
Sleep-wake cycle is characterized by changes in neuronal network activity. However, for the last decade there is increasing evidence that neuroglial interaction may play a role in the modulation of sleep homeostasis and that astrocytes have a critical impact in this process. Interestingly, astrocytes are organized into communicating networks based on their high expression of connexins, which are the molecular constituents of gap junction channels. Thus, neuroglial interactions should also be considered as the result of the interplay between neuronal and astroglial networks. Here, we investigate the effect of modafinil, a wakefulness-promoting agent, on astrocyte gap junctional communication. We report that in the cortex modafinil injection increases the expression of mRNA and protein of connexin 30 but not those of connexin 43, the other major astroglial connexin. These increases are correlated with an enhancement of intercellular dye coupling in cortical astrocytes, which is abolished when neuronal activity is silenced by tetrodotoxin. Moreover, gamma-hydroxybutyric acid, which at a millimolar concentration induces sleep, has an opposite effect on astroglial gap junctions in an activity-independent manner. These results support the proposition that astroglia may play an important role in complex physiological brain functions, such as sleep regulation, and that neuroglial networking interaction is modified during sleep-wake cycle. This article is part of the Special Issue Section entitled 'Current Pharmacology of Gap Junction Channels and Hemichannels'.
睡眠-觉醒周期的特征是神经网络活动的变化。然而，在过去十年中，越来越多的证据表明神经胶质细胞间的相互作用可能在睡眠稳态调节中发挥作用，并且星形胶质细胞在这一过程中具有关键影响。有趣的是，星形胶质细胞基于其高表达的连接蛋白（缝隙连接通道的分子成分）而组织成通讯网络。因此，神经胶质细胞间的相互作用也应被视为神经元网络和星形胶质细胞网络之间相互作用的结果。在此，我们研究促觉醒药物莫达非尼对星形胶质细胞缝隙连接通讯的影响。我们报告，在皮质中注射莫达非尼可增加连接蛋白30的mRNA和蛋白质表达，但不影响另一种主要的星形胶质细胞连接蛋白连接蛋白43的表达。这些增加与皮质星形胶质细胞中细胞间染料偶联的增强相关，当用河豚毒素使神经元活动沉默时，这种增强作用消失。此外，毫摩尔浓度的γ-羟基丁酸可诱导睡眠，它以一种不依赖活动的方式对星形胶质细胞缝隙连接产生相反的作用。这些结果支持以下观点：星形胶质细胞可能在复杂的大脑生理功能（如睡眠调节）中发挥重要作用，并且神经胶质细胞网络相互作用在睡眠-觉醒周期中会发生改变。本文是名为“缝隙连接通道和半通道的当前药理学”的特刊部分的一部分。
