Region-specific dysregulation of glycogen synthase kinase-3β and β-catenin in the postmortem brains of subjects with bipolar disorder and schizophrenia

• Published in: Bipolar disorders Vol. 17; no. 2; pp. 160 - 171
• Main Authors: Pandey, Ghanshyam N, Rizavi, Hooriyah S, Tripathi, Madhulika, Ren, Xinguo
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.03.2015
• Subjects: Adult; Aged; Aged, 80 and over; Base Sequence; beta Catenin - genetics; beta Catenin - metabolism; Bipolar Disorder - genetics; Bipolar Disorder - metabolism; bipolar illness; Brain - metabolism; Case-Control Studies; cingulate gyrus; Female; Glycogen Synthase Kinase 3 - genetics; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; GSK-3β; Gyrus Cinguli - metabolism; Humans; Male; Middle Aged; Molecular Sequence Data; pGSK-3β-ser-9; Phosphoproteins - metabolism; Phosphorylation; postmortem brain; prefrontal cortex; Prefrontal Cortex - metabolism; Real-Time Polymerase Chain Reaction; RNA, Messenger - metabolism; schizophrenia; Schizophrenia - genetics; Schizophrenia - metabolism; Serine - metabolism; Signal Transduction; temporal cortex; Temporal Lobe - metabolism; Wnt Signaling Pathway; β-catenin; GSK-3β; β-catenin; pGSK-3β-ser-9; prefrontal cortex; postmortem brain; bipolar illness; schizophrenia; temporal cortex; cingulate gyrus
• ISSN: 1398-5647; 1399-5618; 1399-5618
• DOI: 10.1111/bdi.12228

Objectives There is both direct and indirect evidence suggesting abnormalities of glycogen synthase kinase (GSK)‐3β and β‐catenin, two important components of the Wingless‐type (Wnt) signaling pathway, in the pathophysiology of bipolar illness and possibly schizophrenia (SZ). In order to further clarify the role of the Wnt signaling pathway in the pathophysiology of bipolar disorder (BP) and SZ, we studied GSK‐3β and β‐catenin in the postmortem brains of subjects with these disorders. Methods We determined the protein expression of GSK‐3β, phosphorylated form at serine 9 position (pGSK‐3‐ser‐9), and β‐catenin using the western blot technique, and mRNA using the quantitative polymerase chain reaction (qPCR) method, in the dorsolateral prefrontal cortex (DLPFC), cingulate gyrus (CG), and temporal cortex (TEMP) obtained from 19 subjects with BP, 20 subjects with SZ, and 20 normal control (NC) subjects. Results We found that the protein expression of GSK‐3β, pGSK‐3β‐ser‐9, and β‐catenin was significantly decreased in the DLPFC and TEMP, but not in the CG, of subjects with BP compared with NC subjects. The mRNA expression of GSK‐3β and β‐catenin was significantly decreased in the DLPFC and TEMP, but not in the CG, of subjects with BP compared with NC subjects. There were no significant differences in the protein or mRNA expression of GSK‐3β, pGSK‐3β‐ser‐9, or β‐catenin between subjects with SZ and NC subjects in any of the brain areas studied. Conclusions These studies show region‐specific abnormalities of both protein and mRNA expression of GSK‐3β and β‐catenin in postmortem brains of subjects with BP but not subjects with SZ. Thus, abnormalities of the Wnt signaling pathway may be associated with the pathophysiology of bipolar illness.