title: Region-specific dysregulation of glycogen synthase kinase-3β and β-catenin in the postmortem brains of subjects with bipolar disorder and schizophrenia.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Ghanshyam N
authors.initials: GN
authors.lastname: Pandey
authors.forename: Hooriyah S
authors.initials: HS
authors.lastname: Rizavi
authors.forename: Madhulika
authors.initials: M
authors.lastname: Tripathi
authors.forename: Xinguo
authors.initials: X
authors.lastname: Ren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D013702:Temporal Lobe / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D010750:Phosphoproteins; D012333:RNA, Messenger; D051176:beta Catenin; D012694:Serine; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: GSK-3β; bipolar illness; cingulate gyrus; pGSK-3β-ser-9; postmortem brain; prefrontal cortex; schizophrenia; temporal cortex; β-catenin