%0 Journal Article %T Microglial production of quinolinic acid as a target and a biomarker of the antidepressant effect of ketamine %+ Neuropathologie expérimentale / Experimental neuropathology %+ CHU Saint-Antoine [AP-HP] %+ Sorbonne Université (SU) %+ Centre Hospitalier Sainte Anne [Paris] %+ Université Paris Descartes - Paris 5 (UPD5) %+ Histopathologie humaine et Modèles animaux %+ BioImagerie Photonique – Photonic BioImaging (UTechS PBI) %+ Institut National de la Santé et de la Recherche Médicale (INSERM) %+ Paris Diderot - Paris 7 - UFR Lettres, Arts, Langues (UPD7 UFR LAC) %+ Service universitaire de psychiatrie d'adultes %+ CHU Pitié-Salpêtrière [AP-HP] %+ Neuro-anesthésiologie et Médecine des soins intensifs [CH Sainte-Anne] (GHU Paris psychiatrie & neurosciences) %+ Service de biochimie et biologie moléculaire %+ Laboratoire Hospitalo-Universitaire de Neuropathologie [Paris] %A Verdonk, Franck %A Petit, Anne-Cécile %A Abdel-Ahad, Pierre %A Vinckier, Fabien %A Jouvion, Gregory %A de Maricourt, Pierre %A de Medeiros, Gabriela Ferreira %A Danckaert, Anne %A van Steenwinckel, Juliette %A Blatzer, Michael %A Maignan, Anna %A Langeron, Olivier %A Sharshar, Tarek %A Callebert, Jacques %A Launay, Jean-Marie %A Chrétien, Fabrice %A Gaillard, Raphael %Z This work was supported by the Fondation des Gueules Cassées, the Comité d’Interface SFAR (Société Française d’Anesthésie-Réanimation), SRLF (Société de Réanimation de Langue Française), INSERM, the Pierre Deniker and the « entreprendre pour aider » foundations. Franck Verdonk received financial support from ANRT (Association Nationale de la Recherche et de la Technologie) through an Air Liquide-CIFRE contract 2012/1315. The Imagopole is part of the France BioImaging infrastructure supported by the French National Research Agency (ANR-10-INSB-04-01, “Investments for the future”) and is grateful for the support from the Conseil de la Region Ile-de-France (program Sesame 2007, project Imagopole, S.L. Shorte). %< avec comité de lecture %@ 0889-1591 %J Brain, Behavior, and Immunity %I Elsevier %V 81 %P 361 - 373 %8 2019-10 %D 2019 %R 10.1016/j.bbi.2019.06.033 %M 31255681 %K Biomarker %K Depression %K Inflammation %K Ketamine %K Microglia %K Murine model %K Quinolinic acid %K Translational research %Z Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/NeurobiologyJournal articles %X Major depressive disorder is a complex multifactorial condition with a so far poorly characterized underlying pathophysiology. Consequently, the available treatments are far from satisfactory as it is estimated that up to 30% of patients are resistant to conventional treatment. Recent comprehensive evidence has been accumulated which suggests that inflammation may be implied in the etiology of this disease. Here we investigated ketamine as an innovative treatment strategy due to its immune-modulating capacities. In a murine model of LPS-induced depressive-like behavior we demonstrated that a single dose of ketamine restores the LPS-induced depressivelike alterations. These behavioral effects are associated with i/ a reversal of anxiety and reduced self-care, ii/ a decrease in parenchymal cytokine production, iii/ a modulation of the microglial reactivity and iv/ a decrease in microglial quinolinic acid production that is correlated with plasmatic peripheral production. In a translational approach, we show that kynurenic acid to quinolinic acid ratio is a predictor of ketamine response in treatmentresistant depressed patients and that the reduction in quinolinic acid after a ketamine infusion is a predictor of the reduction in MADRS score. Our results suggest that microglia is a key therapeutic target and that quinolinic acid is a biomarker of ketamine response in major depressive disorder. %G English %2 https://pasteur.hal.science/pasteur-03263257/document %2 https://pasteur.hal.science/pasteur-03263257/file/1-s2.0-S0889159119304386-main.pdf %L pasteur-03263257 %U https://pasteur.hal.science/pasteur-03263257 %~ INSERM %~ PASTEUR %~ UNIV-PARIS5 %~ UNIV-PARIS7 %~ APHP %~ USPC %~ CHU-UNIV-PARIS5 %~ SORBONNE-UNIVERSITE %~ SORBONNE-UNIV %~ SU-MEDECINE %~ SU-MED %~ UNIV-PARIS %~ TEST-HALCNRS %~ SU-TI %~ ANR %~ ALLIANCE-SU