title: Antidepressants Impact Connexin 43 Channel Functions in Astrocytes.
abstract: Glial cells, and in particular astrocytes, are crucial to maintain neuronal microenvironment by regulating energy metabolism, neurotransmitter uptake, gliotransmission, and synaptic development. Moreover, a typical feature of astrocytes is their high expression level of connexins, a family of membrane proteins that form gap junction channels allowing intercellular exchanges and hemichannels that provide release and uptake pathways for neuroactive molecules. Interestingly, several studies have revealed unexpected changes in astrocytes from depressive patients and rodent models of depressive-like behavior. Moreover, changes in the expression level of the astroglial connexin 43 (Cx43) have been reported in a depressive context. On the other hand, antidepressive drugs have also been shown to impact the expression of this connexin in astrocytes. However, so far there is little information concerning the functional consequence of these changes, i.e., the status of gap junctional communication and hemichannel activity in astrocytes exposed to antidepressants. In the present work we focused our attention on the action of seven antidepressants from four different therapeutic classes and tested their effects on Cx43 expression and on the two connexin-based channels functions studied in cultured astrocytes. We here report that when used at non-toxic and clinically relevant concentrations they have no effects on Cx43 expression but differential effects on Cx43 gap junction channels. Moreover, all tested antidepressants inhibit Cx43 hemichannel with different efficiency depending on their therapeutic classe. By studying the impact of antidepressants on the functional status of astroglial connexin channels, contributing to dynamic neuroglial interactions, our observations should help to better understand the mechanism by which these drugs provide their effect in the brain.
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050Paris, France; University Pierre et Marie CurieParis, France; MemoLife Laboratory of Excellence and Paris Science Lettre Research UniversityParis, France; TheranexusLyon, France.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Jeanson
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050Paris, France; University Pierre et Marie CurieParis, France; MemoLife Laboratory of Excellence and Paris Science Lettre Research UniversityParis, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Pondaven
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050Paris, France; University Pierre et Marie CurieParis, France; MemoLife Laboratory of Excellence and Paris Science Lettre Research UniversityParis, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Ezan
authors.affiliation: Theranexus Lyon, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Mouthon
authors.affiliation: Theranexus Lyon, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Charvériat
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050Paris, France; University Pierre et Marie CurieParis, France; MemoLife Laboratory of Excellence and Paris Science Lettre Research UniversityParis, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Giaume
keywords: depression; gap Junctions; glial cells; hemichannels; inflammation