title: Decreased NR1, NR2A, and SAP102 transcript expression in the hippocampus in bipolar disorder.
abstract: OBJECTIVE
  Schizophrenia is associated with dysfunction of glutamatergic neurotransmission, and several studies have suggested glutamatergic abnormalities in bipolar disorder. Recent data suggest involvement of the NMDA receptor signaling complex, which includes NMDA receptor subunits as well as associated intracellular interacting proteins critical for NMDA receptor assembly, trafficking, and activation; the most well-characterized being PSD93, PSD95, SAP102, and NF-L. Previously, studies from our laboratories have described changes in glutamate receptor subunit transcript and binding site expression in schizophrenia and changes in NMDA receptor binding site expression in bipolar disorder in postmortem brain tissue. In the present work, we focus on the expression of these molecules in hippocampus in schizophrenia and bipolar affective disorder I.
  
  
  METHODS
  We performed in situ hybridization to assess hippocampal expression of the transcripts encoding NMDA receptor subunits NR1, 2A, 2B, 2C and 2D, and the transcripts for the NMDA receptor associated PSD proteins PSD95, PSD93, NF-L, and SAP102 in subjects with schizophrenia, bipolar affective disorder I, and a comparison group. We also measured [(3)H]CGP39653 and [(3)H]MK-801 binding site expression in the hippocampus in schizophrenia.
  
  
  RESULTS
  There was a significant decrease in the expression of transcripts for NR1 and NR2A subunits and SAP102 in bipolar disorder. We did not detect any changes in these transcripts or in binding site expression in the hippocampus in schizophrenia.
  
  
  CONCLUSIONS
  We propose that the NMDA receptor signaling complex, including the intracellular machinery that is coupled to the NMDA receptor subunits, is abnormal in the hippocampus in bipolar disorder. These data suggest that bipolar disorder might be associated with abnormalities of glutamate-linked intracellular signaling and trafficking processes.
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, CIRC 576A 0021, 1530 3rd Avenue South, Birmingham, AL 35294, USA. smithrob@uab.edu
authors.forename: Robert E
authors.initials: RE
authors.lastname: McCullumsmith
authors.forename: Lars V
authors.initials: LV
authors.lastname: Kristiansen
authors.forename: Monica
authors.initials: M
authors.lastname: Beneyto
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Scarr
authors.forename: Brian
authors.initials: B
authors.lastname: Dean
authors.forename: James H
authors.initials: JH
authors.lastname: Meador-Woodruff
mesh_terms: D001665:Binding Sites; D001667:Binding, Competitive / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D011237:Predictive Value of Tests; D017729:Presynaptic Terminals / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D015415:Biomarkers; C116869:DLG3 protein, human; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; D018698:Glutamic Acid