Table 2.
Evidences of the kynurenine pathway in depression from animal studies.
| AUTHOR, YEAR | ANIMAL MODEL | MAIN FINDINGS |
|---|---|---|
| GOUBOUT, 2008 | LPS | Advance in age was associated with depressive-like behavior, elevated peripheral and brain IDO, and turnover rate of brain 5-HT |
| MOREAU, 2005; 2008 | BCG | Depressive-like behavior was correlated with increased levels of TNF-α and peripheral IDO activation |
| DOBOS, 2012 | LPS | IDO inhibitor prevented depressive-like behavior |
| LAUGERAY, 2010 | Chronic stress | KYN/TRP ratio in the periphery was linked to the magnitude of depressive and anxiety-like behaviors |
| CHEN, 2013 | UCMS and QUIN microinjection | Depressive-like behavior, increased levels of glutamate and altered levels of glutamate receptors subunit. Glutamate and QUIN antagonists reversed behavior and neurochemical alterations |
| GIBNEY, 2013 | poly I:C | Depression and anxiety-like behavior, elevated expression pro-inflammatory cytokines, and decreased expression of BDNF and it receptor TrkB in hippocampus and frontal cortex |
| FRANKLIN, 2012 | TRP diet depletion | Depressive-like behavior was correlated with increased levels of KYN and reduced levels of KYNA. Paroxetine treatment reversed these alterations in KYN pathway, but not in depressive behavior |
| ARA, 2012 | Chronic stress | Citalopram treatment exerted antidepressive-like behavior and increased turnover of 5-HT via IDO inhibition in brain |
| ELGARF, 2014 | LPS and CMS | Imipramine and pentoxyphylline were effective to reverse depressive-like behavior and the elevated levels in the hippocampal KYN/TRP ratio and TNF-α gene expression induced by both LPS and CMS |
| GIBNEY, 2014 | Restraint stress | TDO inhibitor attenuated depressive-like behavior and reduced circulating KYN concentrations |
| CORONA, 2013 | CX3CR1−/− and LPS | IDO inhibitor reversed neuroinflammation and depressive-like behavior |
| LAWSON, 2013 | LPS | Genetic deletion or pharmacological inhibition of IDO1 attenuated anhedonic behavior |
| O’CONNOR, 2009C | LPS | Minocycline and 1-MT exhibited antidepressant-like behavior and regulated KYN/TRP ratio in the plasma and brain |
| XIE, 2014 | Epilepsy | Minocycline and 1-MT normalized KYN/TRP and 5-HT/TRP ratio and prevented depressive-like behavior |
Legend: 5-HT = 5-hydroxytryptamine serotonin; CMS = Chronic mild stress; CX3CR1−/− = fractalkine receptor deficient; IDO = Indoleamine 2,3 dioxygenase; BCG = Bacillus Calmette-Guérin; BDNF = brain-derived neurotrophic factor; KYNA = kynurenic acid; KYN = kynurenine; LPS = lipopolysaccharide; QUIN = Quinolinic acid; TDO = tryptophan 2,3-dioxygenase; TNF-α = tumor necrosis factor alpha; TRP = Catabolizes L-tryptophan; UCMS = unpredictable chronic mild stress.