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Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice

O'CONNOR, J. C ; LAWSON, M. A ; ANDRE, C ; MOREAU, M ; LESTAGE, J ; CASTANON, N ; KELLEY, K. W ; DANTZER, R

Molecular psychiatry, 2009-05, Vol.14 (5), p.511-522 [Periódico revisado por pares]

Basingstoke: Nature Publishing Group

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Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice
Autor: O'CONNOR, J. C ; LAWSON, M. A ; ANDRE, C ; MOREAU, M ; LESTAGE, J ; CASTANON, N ; KELLEY, K. W ; DANTZER, R
Assuntos: Adult and adolescent clinical studies ; Animal sciences ; Animals ; Antibiotics ; Behavior ; Behavior, Animal - drug effects ; Biological and medical sciences ; Chromatography, High Pressure Liquid ; Comorbidity ; Cytokines ; Cytokinins - metabolism ; Depression ; Depression - blood ; Depression - chemically induced ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Enzyme Activation - drug effects ; Enzyme Inhibitors - pharmacology ; Enzyme Inhibitors - therapeutic use ; Enzymes ; Gene Expression Regulation - drug effects ; Hindlimb Suspension - methods ; Immune system ; Immunotherapy ; Indoleamine-Pyrrole 2,3,-Dioxygenase - antagonists & inhibitors ; Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics ; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism ; Inflammation ; Inflammatory diseases ; Kynurenine - adverse effects ; Kynurenine - blood ; Laboratory animals ; Life Sciences ; Lipopolysaccharides ; Lipopolysaccharides - pharmacology ; Male ; Medical sciences ; Mice ; Mice, Inbred ICR ; Minocycline ; Minocycline - pharmacology ; Minocycline - therapeutic use ; Mood disorders ; Motor Activity - drug effects ; Multiple sclerosis ; Primates ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Rheumatoid arthritis ; Serotonin ; Swimming ; Time Factors ; Tryptophan - analogs & derivatives ; Tryptophan - blood ; Tryptophan - pharmacology ; Tryptophan - therapeutic use ; Tryptophan 2,3-dioxygenase
É parte de: Molecular psychiatry, 2009-05, Vol.14 (5), p.511-522
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
PMCID: PMC2683474
Descrição: Although elevated activity of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) has been proposed to mediate comorbid depression in inflammatory disorders, its causative role has never been tested. We report that peripheral administration of lipopolysaccharide (LPS) activates IDO and culminates in a distinct depressive-like behavioral syndrome, measured by increased duration of immobility in both the forced-swim and tail suspension tests. Blockade of IDO activation either indirectly with the anti-inflammatory tetracycline derivative minocycline, that attenuates LPS-induced expression of proinflammatory cytokines, or directly with the IDO antagonist 1-methyltryptophan (1-MT), prevents development of depressive-like behavior. Both minocycline and 1-MT normalize the kynurenine/tryptophan ratio in the plasma and brain of LPS-treated mice without changing the LPS-induced increase in turnover of brain serotonin. Administration of L-kynurenine, a metabolite of tryptophan that is generated by IDO, to naive mice dose dependently induces depressive-like behavior. These results implicate IDO as a critical molecular mediator of inflammation-induced depressive-like behavior, probably through the catabolism of tryptophan along the kynurenine pathway.
Editor: Basingstoke: Nature Publishing Group
Idioma: Inglês

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Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice

O'CONNOR, J. C ; LAWSON, M. A ; ANDRE, C ; MOREAU, M ; LESTAGE, J ; CASTANON, N ; KELLEY, K. W ; DANTZER, R

Basingstoke: Nature Publishing Group

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