Attenuated Levels of Hippocampal Connexin 43 and its Phosphorylation Correlate with Antidepressant- and Anxiolytic-Like Activities in Mice.

Détails

Ressource 1Télécharger: fncel-09-00490.pdf (1456.63 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_7D7CD0582F9C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Attenuated Levels of Hippocampal Connexin 43 and its Phosphorylation Correlate with Antidepressant- and Anxiolytic-Like Activities in Mice.
Périodique
Frontiers in Cellular Neuroscience
Auteur(s)
Quesseveur G., Portal B., Basile J.A., Ezan P., Mathou A., Halley H., Leloup C., Fioramonti X., Déglon N., Giaume C., Rampon C., Guiard B.P.
ISSN
1662-5102 (Electronic)
ISSN-L
1662-5102
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
9
Pages
490
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: epublish
Résumé
Clinical and preclinical studies have implicated glial anomalies in major depression. Conversely, evidence suggests that the activity of antidepressant drugs is based, at least in part, on their ability to stimulate density and/or activity of astrocytes, a major glial cell population. Despite this recent evidence, little is known about the mechanism(s) by which astrocytes regulate emotionality. Glial cells communicate with each other through gap junction channels (GJCs), while they can also directly interact with neurons by releasing gliotransmitters in the extracellular compartment via an hemichannels (HCs)-dependent process. Both GJCs and HCs are formed by two main protein subunits: connexins (Cx) 30 and 43 (Cx30 and Cx43). Here we investigate the role of hippocampal Cx43 in the regulation of depression-like symptoms using genetic and pharmacological approaches. The first aim of this study was to evaluate the impact of the constitutive knock-down of Cx43 on a set of behaviors known to be affected in depression. Conversely, the expression of Cx43 was assessed in the hippocampus of mice subjected to prolonged corticosterone (CORT) exposure, given either alone or in combination with an antidepressant drug, the selective serotonin reuptake inhibitor fluoxetine. Our results indicate that the constitutive deficiency of Cx43 resulted in the expression of some characteristic hallmarks of antidepressant-/anxiolytic-like behavioral activities along with an improvement of cognitive performances. Moreover, in a new cohort of wild-type mice, we showed that CORT exposure elicited anxiety and depression-like abnormalities that were reversed by chronic administration of fluoxetine. Remarkably, CORT also increased hippocampal amounts of phosphorylated form of Cx43 whereas fluoxetine treatment normalized this parameter. From these results, we envision that antidepressant drugs may exert their therapeutic activity by decreasing the expression and/or activity of Cx43 resulting from a lower level of phosphorylation in the hippocampus.
Pubmed
Web of science
Création de la notice
11/01/2016 18:22
Dernière modification de la notice
03/03/2018 18:39
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