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EXPRESSION OF KYNURENINE PATHWAY ENZYME TRYPTOPHAN 2,3-DIOXYGENASE IS INCREASED IN THE FRONTAL CORTEX OF INDIVIDUALS WITH SCHIZOPHRENIA

Neurobiol Dis 2004 Apr;15(3):618-29

CL Miller, IC Llenos, JR Dulay, MM Barillo, RY Yolken, S Weis

Abstract

Markers of the kynurenine pathway were studied in postmortem frontal cortex obtained from individuals with schizophrenia and controls. Quantitative endpoint RT-PCR was used to measure mRNA transcripts. One of the two enzymes capable of catalyzing the first step in the pathway, tryptophan 2,3-dioxygenase (TDO2) and indoleamine dioxygense (IDO), the concentration of mRNA for TDO2 was found to be elevated 1.6-fold in the schizophrenia group (P = 0.03), whereas the concentration of the mRNA for IDO was not significantly different between the schizophrenia and control groups. Immunohistochemistry showed an increased density of TD02-immunopositive astroglial cells in the white matter of patients with schizophrenia (P = 0.04). Neurons and vessels were also immunopositive for TDO2, but there were no significant differences in labeling of these structures between the two groups. These results add to the evidence that kynurenine pathway changes might be involved in the pathogenesis of schizophrenia and the schizophrenia-like psychoses of other disorder.

 

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