Alteration of cyclic-AMP response element binding protein in the postmortem brain of subjects with bipolar disorder and schizophrenia

• Published in: Journal of affective disorders Vol. 152-154; pp. 326 - 333
• Main Authors: Ren, Xinguo, Rizavi, Hooriyah S., Khan, Mansoor A., Bhaumik, Runa, Dwivedi, Yogesh, Pandey, Ghanshyam N.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.01.2014; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Aged; Aged, 80 and over; Biological and medical sciences; Bipolar affective disorder; Bipolar disorder; Bipolar Disorder - metabolism; Bipolar disorders; Blotting, Western; Brain - metabolism; Camps; Case-Control Studies; Cingulate gyrus; Cortex; CRE-DNA binding activity; CREB; Cyclic AMP Response Element-Binding Protein - metabolism; Female; Human DLPFC; Humans; Male; Medical sciences; Middle Aged; Miscellaneous; Mood disorders; Postmortems; Proteins; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Real-Time Polymerase Chain Reaction; Schizophrenia; Schizophrenia - metabolism; Human DLPFC; Schizophrenia; Bipolar disorder; CREB; CRE-DNA binding activity; Cingulate gyrus; Mood disorder; Human; Central nervous system; Postmortem; Activity; Encephalon; Psychosis; Dorsolateral prefrontal cortex; Cingulate cortex; DNA; Transcription factor CREB
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2013.09.033

Abnormalities of cyclic-AMP (cAMP) response element binding protein (CREB) function has been suggested in bipolar (BP) illness and schizophrenia (SZ), based on both indirect and direct evidence. To further elucidate the role of CREB in these disorders, we studied CREB expression and function in two brain areas implicated in these disorders, i.e., dorsolateral prefrontal cortex (DLPFC) and cingulate gyrus (CG). We determined CREB protein expression using Western blot technique, CRE-DNA binding using gel shift assay, and mRNA expression using real-time RT-polymerase chain reaction (qPCR) in DLPFC and CG of the postmortem brain of BP (n=19), SZ (n=20), and normal control (NC, n=20) subjects. We observed that CREB protein and mRNA expression and CRE-DNA binding activity were significantly decreased in the nuclear fraction of DLPFC and CG obtained from BP subjects compared with NC subjects. However, the protein and mRNA expression and CRE-DNA binding in SZ subjects was significantly decreased in CG, but not in DLPFC, compared with NC. These studies thus indicate region-specific abnormalities of CREB expression and function in both BP and SZ. They suggest that abnormalities of CREB in CG may be associated with both BP and SZ, but its abnormality in DLPFC is specific to BP illness.