The high-affinity niacin receptor HM74A is decreased in the anterior cingulate cortex of individuals with schizophrenia.
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.
Miller
Christine L
CL
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21287, USA. jemanget@yahoo.com
Dulay
Jeannette R
JR
D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000378:metabolism; D011180:Postmortem Changes; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
C530636:HCAR2 protein, human; C473653:HCAR3 protein, human; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D009525:Niacin