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The role of indoleamine 2,3-dioxygenase in a mouse model of neuroinflammation-induced depression

Dobos, N., de Vries, E. F. J., Kema, I. P., Patas, K., Prins, M., Nijholt, I. M., Dierckx, R. A., Korf, J., den Boer, J. A., Luiten, P. G. M. & Eisel, U. L. M., 2012, In : Journal of alzheimers disease. 28, 4, p. 905-915 11 p.

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  • The Role of Indoleamine 2,3-Dioxygenase in a Mouse Model of Neuroinflammation-Induced Depression

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DOI

Indoleamine 2,3-dioxygenase (IDO), an enzyme which is activated by pro-inflammatory cytokines, has been suggested as a potential link between neuroinflammatory processes in neurodegenerative diseases (like Alzheimer's disease) and depression. The present study aimed to determine whether neuroinflammation-induced increased IDO levels in the mammalian brain will lead to depressive-like behavior. Neuroinflammation was initiated in mice by a single intracerebroventricular injection of lipopolysaccharide (LPS). Cerebral inflammation was monitored 1, 2, 3 and 4 days after the injection with small-animal positron emission tomography (PET) using the inflammatory marker [C-11]-PK11195. In the presence or absence of systemically applied 1-methyl-tryptophan (1-MT), a competitive IDO-inhibitor, we assessed the development of depressive-like behavioral symptoms in parallel with IDO expression and activity. The PK11195 PET signal reached a highly significant peak 3 days after LPS injection, while these animals displayed a significant increase of depressive-like behavior in the forced swim test compared to vehicle-injected animals. These findings were paralleled by a significant increase of IDO in the brainstem, and an increased kynurenine/tryptophan ratio in the serum. Moreover, we report here for the first time, that inhibition of IDO by 1-MT in centrally induced neuroinflammation under experimental conditions can prevent the development of depressive-like behavior.

Original languageEnglish
Pages (from-to)905-915
Number of pages11
JournalJournal of alzheimers disease
Volume28
Issue number4
Publication statusPublished - 2012

    Keywords

  • Depression, indoleamine 2,3-dioxygenase, lipopolysaccharide, neuroinflammation, positron emission tomography, ALZHEIMERS-DISEASE, MAJOR DEPRESSION, CALMETTE-GUERIN, 2,3 DIOXYGENASE, IMMUNE-SYSTEM, RISK-FACTOR, IN-VIVO, BRAIN, LIPOPOLYSACCHARIDE, BEHAVIOR

ID: 5508183