title: The role of indoleamine 2,3-dioxygenase in a mouse model of neuroinflammation-induced depression.
abstract: 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 [(11)C]-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.
authors: Department of Molecular Neurobiology, University of Groningen, Groningen, The Netherlands.
authors: Nikoletta
authors: N
authors: Dobos
authors: Erik F J
authors: EF
authors: de Vries
authors: Ido P
authors: IP
authors: Kema
authors: Konstantinos
authors: K
authors: Patas
authors: Marloes
authors: M
authors: Prins
authors: Ingrid M
authors: IM
authors: Nijholt
authors: Rudi A
authors: RA
authors: Dierckx
authors: Jakob
authors: J
authors: Korf
authors: Johan A
authors: JA
authors: den Boer
authors: Paul G M
authors: PG
authors: Luiten
authors: Ulrich L M
authors: UL
authors: Eisel
mesh_terms: D000818:Animals; D003863:Depression / Q000201:enzymology* / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D004660:Encephalitis / Q000150:complications / Q000201:enzymology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014364:Tryptophan