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Abstract
The pathway for de novo synthesis of the suite of niacin congeners, the kynurenine
pathway, has been shown to be upregulated in prior studies of postmortem brain tissue
from individuals with schizophrenia. The cause of the upregulation is unknown, but
one factor may be a defect in feedback regulation via receptors responsive to niacin.
A high-affinity and low-affinity receptor for niacin have been identified, HM74A and
HM74, respectively. We used RT-QPCR and Western blots to quantify expression of HM74A
and HM74 receptors in brain tissue obtained postmortem from patients with schizophrenia
(N=12) or bipolar disorder (N=14) and from normal controls (N=14). Although the protein
for the HM74 receptor was unchanged, the protein for HM74A was significantly decreased
in the schizophrenia group, both when normalized to GAPDH protein or to HM74 as an
internal control for degradation and gel-loading error (0.56-fold+/-0.36, p=0.016
and 0.58-fold+/-0.19 the mean control value, p=0.001, respectively). In contrast,
the transcript for HM74A was significantly increased, revealing a striking dysregulation
between gene transcription and final protein product. No significant differences in
HM74A were found for the bipolar group relative to controls. These results are consistent
with the blunted niacin flush response reported for individuals with schizophrenia
and may be relevant to different rates of comorbid disease.