Maternal immune activation in rats blunts brain cytokine and kynurenine pathway responses to a second immune challenge in early adulthood

Publication date: Available online 27 September 2018Source: Progress in Neuro-Psychopharmacology and Biological PsychiatryAuthor(s): Sarah M. Clark, Francesca M. Notarangelo, Xin Li, Shuo Chen, Robert Schwarcz, Leonardo H. TonelliAbstractMaternal immune activation (MIA) with the viral mimic poly I:C provides an established rodent model for studying schizophrenia (SZ) and other human neurodevelopmental disorders. Postnatal infections are additional risk factors in SZ and may cumulatively contribute to the emergence of pathophysiology. Underlying mechanisms may involve metabolites of the kynurenine pathway (KP) of tryptophan degradation, which is readily induced by inflammatory stimuli. Here we compared the expression of selected cytokines and KP enzymes, and the levels of selected KP metabolites, in the brain of MIA offspring following a second, acute immune challenge with lipopolysaccharides (LPS) on postnatal day (PND) 35 (adolescence) or PND 60 (early adulthood). Assessed in adolescence, MIA did not alter the expression of pro-inflammatory cytokines (except TNF-α) or KP metabolite levels compared to controls, but substantially reduced the expression of the anti-inflammatory cytokines IL-4 and IL-10 and influenced the expression of two of the four KP enzymes examined (IDO1 and TDO2). LPS treatment caused distinct changes in the expression of pro- and anti-inflammatory cytokines, as well as KP enzymes in MIA offspring, but had no effect on KP metabolites compared to control ...
Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - Category: Psychiatry Source Type: research