The psychostimulant modafinil enhances gap junctional communication in cortical astrocytes

Autor: Liu Xe, Petit Jean-Marie, Ezan P., Gyger J., Magistretti Pierre J., Giaume C.
Zdroj: Neuropharmacology
Popis: 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'.
Databáze: OpenAIRE