Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia.
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. Of the two enzymes capable of catalyzing the first step in the pathway, tryptophan 2,3-dioxygenase (TDO2) and indoleamine dioxygenase (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 TDO2-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 disorders.
Miller
Christine L
CL
Stanley Division for Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21287, USA. Cmiller2@jhmi.edu
Llenos
Ida C
IC
Dulay
Jeanette R
JR
Barillo
Meliza M
MM
Yolken
Robert H
RH
Weis
Serge
S
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D049308:Dioxygenases; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005625:Frontal Lobe / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010105:Oxygenases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000201:enzymology*; D012907:Smoking; D014366:Tryptophan Oxygenase / Q000096:biosynthesis*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D007737:Kynurenine; D010105:Oxygenases; D049308:Dioxygenases; D014366:Tryptophan Oxygenase