PMID- 26733815 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160106 LR - 20201001 IS - 1662-5102 (Print) IS - 1662-5102 (Electronic) IS - 1662-5102 (Linking) VI - 9 DP - 2015 TI - Attenuated Levels of Hippocampal Connexin 43 and its Phosphorylation Correlate with Antidepressant- and Anxiolytic-Like Activities in Mice. PG - 490 LID - 10.3389/fncel.2015.00490 [doi] LID - 490 AB - 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. FAU - Quesseveur, Gael AU - Quesseveur G AD - Institut National de la Sante et de la Recherche Medicale UMR-S 1178 - Depression, Plasticite and Resistance Aux Antidepresseurs, Laboratoire de Neuropharmacologie EA 3544, Faculte de Pharmacie, Universite Paris-Sud Chatenay-Malabry, France. FAU - Portal, Benjamin AU - Portal B AD - Centre National de la Recherche Scientifique, Centre de Recherches sur la Cognition Animale UMR 5169, Centre de Biologie Integrative, Universite Toulouse III- Paul Sabatier Toulouse, France. FAU - Basile, Jean-Arnaud AU - Basile JA AD - Centre National de la Recherche Scientifique, Centre de Recherches sur la Cognition Animale UMR 5169, Centre de Biologie Integrative, Universite Toulouse III- Paul Sabatier Toulouse, France. FAU - Ezan, Pascal AU - Ezan P AD - Center for Interdisciplinary Research in Biology, Centre National de la Recherche Scientifique UMR 7241, College de France Paris, France. FAU - Mathou, Alexia AU - Mathou A AD - Centre des Sciences du Gout et de l'Alimentation - Centre National de la Recherche Scientifique UMR 6265 - Institut National de la Recherche Agronomique UMR 1324, Universite de Bourgogne Dijon, France. FAU - Halley, Helene AU - Halley H AD - Centre National de la Recherche Scientifique, Centre de Recherches sur la Cognition Animale UMR 5169, Centre de Biologie Integrative, Universite Toulouse III- Paul Sabatier Toulouse, France. FAU - Leloup, Corinne AU - Leloup C AD - Centre des Sciences du Gout et de l'Alimentation - Centre National de la Recherche Scientifique UMR 6265 - Institut National de la Recherche Agronomique UMR 1324, Universite de Bourgogne Dijon, France. FAU - Fioramonti, Xavier AU - Fioramonti X AD - Centre des Sciences du Gout et de l'Alimentation - Centre National de la Recherche Scientifique UMR 6265 - Institut National de la Recherche Agronomique UMR 1324, Universite de Bourgogne Dijon, France. FAU - Deglon, Nicole AU - Deglon N AD - Laboratory of Cellular and Molecular Neurotherapies, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois Lausanne, Switzerland. FAU - Giaume, Christian AU - Giaume C AD - Center for Interdisciplinary Research in Biology, Centre National de la Recherche Scientifique UMR 7241, College de France Paris, France. FAU - Rampon, Claire AU - Rampon C AD - Centre National de la Recherche Scientifique, Centre de Recherches sur la Cognition Animale UMR 5169, Centre de Biologie Integrative, Universite Toulouse III- Paul Sabatier Toulouse, France. FAU - Guiard, Bruno P AU - Guiard BP AD - Institut National de la Sante et de la Recherche Medicale UMR-S 1178 - Depression, Plasticite and Resistance Aux Antidepresseurs, Laboratoire de Neuropharmacologie EA 3544, Faculte de Pharmacie, Universite Paris-SudChatenay-Malabry, France; Centre National de la Recherche Scientifique, Centre de Recherches sur la Cognition Animale UMR 5169, Centre de Biologie Integrative, Universite Toulouse III- Paul SabatierToulouse, France. LA - eng PT - Journal Article DEP - 20151222 PL - Switzerland TA - Front Cell Neurosci JT - Frontiers in cellular neuroscience JID - 101477935 PMC - PMC4686612 OTO - NOTNLM OT - antidepressants OT - anxiety OT - astrocytes OT - behavior OT - connexin 43 OT - depression OT - hippocampus OT - stress EDAT- 2016/01/07 06:00 MHDA- 2016/01/07 06:01 PMCR- 2015/01/01 CRDT- 2016/01/07 06:00 PHST- 2015/10/23 00:00 [received] PHST- 2015/12/03 00:00 [accepted] PHST- 2016/01/07 06:00 [entrez] PHST- 2016/01/07 06:00 [pubmed] PHST- 2016/01/07 06:01 [medline] PHST- 2015/01/01 00:00 [pmc-release] AID - 10.3389/fncel.2015.00490 [doi] PST - epublish SO - Front Cell Neurosci. 2015 Dec 22;9:490. doi: 10.3389/fncel.2015.00490. eCollection 2015.