Abnormalities in the dopamine system in schizophrenia may lie in altered levels of dopamine receptor-interacting proteins.
BACKGROUND
Dopamine receptor-interacting proteins constitute a part of the dopamine system that is involved in regulation of dopamine receptor-associated intracellular signaling. Previously, we demonstrated that two such proteins, the D1 receptor-interacting protein calcyon and the D2 receptor-interacting protein neuronal calcium sensor-1 (NCS-1), were elevated in the prefrontal cortex of schizophrenia cases from the Stanley Foundation Neuropathology Consortium.


METHODS
The aim of this study was to confirm and expand these findings. We employed Western blot and real-time reverse transcriptase polymerase chain reaction analyses to compare prefrontal (area 46) and occipital (area 17) cortical levels of calcyon and NCS-1 proteins and mRNAs between schizophrenia (n = 37) and control (n = 30) cohorts from the Brain Collection of the Mount Sinai Medical School/Bronx Veterans Administration Medical Center.


RESULTS
The schizophrenia cohort showed significant up-regulation of calcyon protein and message levels in both prefrontal and occipital cortical regions, both of which also displayed schizophrenia-associated up-regulation of NCS-1 message. Protein levels of NCS-1 were elevated only in the prefrontal cortex. All increases in protein levels were correlated with those of corresponding messages. Furthermore, schizophrenia-associated alterations in the levels of calcyon and NCS-1 messages were correlated.


CONCLUSIONS
Up-regulation of calcyon and NCS-1 in the second schizophrenia cohort strengthens the proposition that abnormalities of the dopamine system in this disease may lie in altered levels of dopamine receptor-interacting proteins. Also, up-regulation of both calcyon and NCS-1 in the cortex of schizophrenia patients can be attributed largely to an enhanced transcription or reduced degradation of their messages. Finally, our findings suggest that elevations in the expressions of calcyon and NCS-1 in schizophrenia may have the same underlying cause.
Bai
Jie
J
Department of Biomedical Sciences, University of Maryland, Baltimore, Maryland 21201, USA.
He
Fang
F
Novikova
Svetlana I
SI
Undie
Ashiwel S
AS
Dracheva
Stella
S
Haroutunian
Vahram
V
Lidow
Michael S
MS
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D015331:Cohort Studies; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008253:Macaca mulatta; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D011954:Receptors, Dopamine; C405464:calcyon; C101464:frequenin calcium sensor proteins; D006220:Haloperidol; D004298:Dopamine