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

Nikoletta Dobos, Erik F.J. de Vries, Ido P. Kema, Konstantinos Patas, Marloes Prins, Ingrid M. Nijholt, Rudi A. Dierckx, Jakob Korf, Johan A. den Boer, Paul G M Luiten, Ulrich L M Eisel*

*Bijbehorende auteur voor dit werk



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 [11C]-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.

Originele taal-2English
TitelHandbook of Depression in Alzheimer's Disease
RedacteurenGwenn S. Smith
UitgeverijIOS Press
Aantal pagina's11
ISBN van elektronische versie9781614995418
StatusPublished - 2015

Publicatie series

NaamAdvances in Alzheimer's Disease
ISSN van geprinte versie22105727
ISSN van elektronische versie22105735

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