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© Uwe Maskos
Tranche d'hippocampe de souris colorée avec deux toxines spécifiques de sous-types de récepteur nicotinique, en rouge (grains), et en vert (corps cellulaires). L'hippocampe est la zone du cerveau qui gère la mémoire spatiale.
Publication : Brain, behavior, and immunity

Microglial production of quinolinic acid as a target and a biomarker of the antidepressant effect of ketamine.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Brain, behavior, and immunity - 01 Oct 2019

Verdonk F, Petit AC, Abdel-Ahad P, Vinckier F, Jouvion G, de Maricourt P, De Medeiros GF, Danckaert A, Van Steenwinckel J, Blatzer M, Maignan A, Langeron O, Sharshar T, Callebert J, Launay JM, Chrétien F, Gaillard R,

Link to Pubmed [PMID] – 31255681

Link to DOI – S0889-1591(19)30438-610.1016/j.bbi.2019.06.033

2019 10; 81(): 361-373

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 depressive-like 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 treatment-resistant 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.