title: [Gap junctions: A new therapeutic target in major depressive disorder?].
abstract: Major depressive disorder is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and is associated with excess mortality, especially from cardiovascular diseases and through suicide. The treatments of this disease with tricyclic antidepressants and monoamine oxidase inhibitors are poorly tolerated and those that selectively target serotonin and norepinephrine re-uptake are not effective in all patients, showing the need to find new therapeutic targets. Post-mortem studies of brains from patients with major depressive disorders described a reduced expression of the gap junction-forming membrane proteins connexin 30 and connexin 43 in the prefrontal cortex and the locus coeruleus. The use of chronic unpredictable stress, a rodent model of depression, suggests that astrocytic gap junction dysfunction contributes to the pathophysiology of major depressive disorder. Chronic treatments of rats with fluoxetine and of rat cultured cortical astrocytes with amitriptyline support the hypothesis that the upregulation of gap junctional intercellular communication between brain astrocytes could be a novel mechanism for the therapeutic effect of antidepressants. In conclusion, astrocytic gap junctions are emerging as a new potential therapeutic target for the treatment of patients with major depressive disorder.
authors: Laboratoire de physiologie humaine, faculté de médecine et pharmacie, université de Poitiers, 6, rue de la Milétrie, bâtiment D1, TSA 51115, 86073 Poitiers cedex 9, France. Electronic address: Denis.Sarrouilhe@univ-poitiers.fr.
authors: D
authors: D
authors: Sarrouilhe
authors: Service de pharmacie, pavillon Janet, centre hospitalier Henri-Laborit, 370, avenue Jacques-Cœur, 86021 Poitiers cedex, France.
authors: C
authors: C
authors: Dejean
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D017629:Gap Junctions / Q000235:genetics / Q000473:pathology*; D006801:Humans
chemical_list: D000928:Antidepressive Agents
keywords: Antidepressive agents; Antidépresseurs; Astrocytes; Cortex préfrontal; Depressive disorder; Gap junctions; Jonctions gap; Prefrontal cortex; Troubles dépressifs