Impact of pro-inflammatory cytokines on glucocorticoid sensitivity, kynurenine pathway and serotonin transport in microglia : implications for depression and the anti-inflammatory actions of antidepressants

Abstract

Neuroinflammation is known to be a major contributing factor to neurodegeneration and has been implicated in neuropsychiatric diseases such as major depression. Microglia are the immunocompetent cells of the CNS and are the main source of inflammatory cytokines in the brain. In the present investigation three potential mechanisms linking inflammatory mediators to microglial activation and function of relevance to neuropsychiatric disorders were explored namely (i) glucocorticoid (GC) signalling (ii) activation of tryptophan metabolism through the kynurenine pathway (KP) and (iii) monoamine transport and metabolism.