title: The psychostimulant modafinil enhances gap junctional communication in cortical astrocytes.
abstract: 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'.
authors.affiliation: 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.
authors.forename: Xinhe
authors.initials: X
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Petit
authors.affiliation: 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.
authors.forename: Pascal
authors.initials: P
authors.lastname: Ezan
authors.affiliation: Laboratory of Neuroenergetic and Cellular Dynamics, Brain Mind Institute, Life Science Faculty, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Joël
authors.initials: J
authors.lastname: Gyger
authors.affiliation: 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.
authors.forename: Pierre
authors.initials: P
authors.lastname: Magistretti
authors.affiliation: 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. Electronic address: christian.giaume@college-de-france.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Giaume
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002491:Central Nervous System Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000166:cytology*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D017629:Gap Junctions / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006885:Hydroxybutyrates / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D000077408:Modafinil; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D001559:Benzhydryl Compounds; D002491:Central Nervous System Agents; D017630:Connexins; D006885:Hydroxybutyrates; D012333:RNA, Messenger; C111420:4-hydroxybutyric acid; D000077408:Modafinil
keywords: Astrocytes; Connexins; Gap junctions; Glia; Modafinil; Sleep