Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8479038 | Neurochemistry International | 2016 | 35 Pages |
Abstract
To quantify the full range of tryptophan metabolites along the kynurenine pathway, a liquid chromatography - tandem mass spectrometry method was developed and used to analyse brain extracts of rodents treated with the kynurenine-3-mono-oxygenase (KMO) inhibitor Ro61-8048 during pregnancy. There were significant increases in the levels of kynurenine, kynurenic acid, anthranilic acid and 3-hydroxy-kynurenine (3-HK) in the maternal brain after 5Â h but not 24Â h, while the embryos exhibited high levels of kynurenine, kynurenic acid and anthranilic acid after 5Â h which were maintained at 24Â h post-treatment. At 24Â h there was also a strong trend to an increase in quinolinic acid levels (PÂ =Â 0.055). No significant changes were observed in any of the other kynurenine metabolites. The results confirm the marked increase in the accumulation of some neuroactive kynurenines when KMO is inhibited, and re-emphasise the potential importance of changes in anthranilic acid. The prolonged duration of metabolite accumulation in the embryo brains indicates a trapping of compounds within the embryonic CNS independently of maternal levels. When brains were examined from young mice heterozygous for the meCP2 gene - a potential model for Rett syndrome - no differences were noted from control mice, suggesting that the proposed roles for kynurenines in autism spectrum disorder are not relevant to Rett syndrome, supporting its recognition as a distinct, independent, condition.
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Authors
Caroline M. Forrest, Peter G.E. Kennedy, Jean Rodgers, R. Neil Dalton, Charles Turner, L. Gail Darlington, Stuart R. Cobb, Trevor W. Stone,