Attenuated Levels of Hippocampal Connexin 43 and its Phosphorylation Correlate with Antidepressant- and Anxiolytic-Like Activities in Mice
Front. Cell. Neurosci.. 2015-12-22; 9:
DOI: 10.3389/fncel.2015.00490
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1. Front Cell Neurosci. 2015 Dec 22;9:490. doi: 10.3389/fncel.2015.00490.
eCollection 2015.
Attenuated Levels of Hippocampal Connexin 43 and its Phosphorylation Correlate
with Antidepressant- and Anxiolytic-Like Activities in Mice.
Quesseveur G(1), Portal B(2), Basile JA(2), Ezan P(3), Mathou A(4), Halley H(2),
Leloup C(4), Fioramonti X(4), Déglon N(5), Giaume C(3), Rampon C(2), Guiard
BP(6).
Author information:
(1)Institut National de la Santé et de la Recherche Médicale UMR-S 1178 –
Dépression, Plasticité and Résistance Aux Antidépresseurs, Laboratoire de
Neuropharmacologie EA 3544, Faculté de Pharmacie, Université Paris-Sud
Châtenay-Malabry, France.
(2)Centre National de la Recherche Scientifique, Centre de Recherches sur la
Cognition Animale UMR 5169, Centre de Biologie Intégrative, Université Toulouse
III- Paul Sabatier Toulouse, France.
(3)Center for Interdisciplinary Research in Biology, Centre National de la
Recherche Scientifique UMR 7241, Collège de France Paris, France.
(4)Centre des Sciences du Goût et de l’Alimentation – Centre National de la
Recherche Scientifique UMR 6265 – Institut National de la Recherche Agronomique
UMR 1324, Université de Bourgogne Dijon, France.
(5)Laboratory of Cellular and Molecular Neurotherapies, Department of Clinical
Neurosciences, Centre Hospitalier Universitaire Vaudois Lausanne, Switzerland.
(6)Institut National de la Santé et de la Recherche Médicale UMR-S 1178 –
Dépression, Plasticité and Résistance Aux Antidépresseurs, Laboratoire de
Neuropharmacologie EA 3544, Faculté de Pharmacie, Université
Paris-SudChâtenay-Malabry, France; Centre National de la Recherche Scientifique,
Centre de Recherches sur la Cognition Animale UMR 5169, Centre de Biologie
Intégrative, Université Toulouse III- Paul SabatierToulouse, France.
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.
DOI: 10.3389/fncel.2015.00490
PMCID: PMC4686612
PMID: 26733815