title: Postsynaptic density levels of the NMDA receptor NR1 subunit and PSD-95 protein in prefrontal cortex from people with schizophrenia.
abstract: BACKGROUND
  There is converging evidence of involvement of N-methyl-d-aspartate (NMDA) receptor hypofunction in the pathophysiology of schizophrenia. Our group recently identified a decrease in total NR1 mRNA and protein expression in the dorsolateral prefrontal cortex in a case-control study of individuals with schizophrenia (n=37/group). The NR1 subunit is critical to NMDA receptor function at the postsynaptic density, a cellular structure rich in the scaffolding protein, PSD-95. The extent to which the NMDA receptor NR1 subunit is altered at the site of action, in the postsynaptic density, is not clear.
  
  
  OBJECTIVE
  To extend our previous results by measuring levels of NR1 and PSD-95 protein in postsynaptic density-enriched fractions of prefrontal cortex from the same individuals in the case-control study noted above.
  
  
  METHODS
  Postsynaptic density-enriched fractions were isolated from fresh-frozen prefrontal cortex (BA10) and subjected to western blot analysis for NR1 and PSD-95.
  
  
  RESULTS
  We found a 20% decrease in NR1 protein (t(66)=-2.874, P=0.006) and a 30% decrease in PSD-95 protein (t(63)=-2.668, P=0.010) in postsynaptic density-enriched fractions from individuals with schizophrenia relative to unaffected controls.
  
  
  CONCLUSIONS
  Individuals with schizophrenia have less NR1 protein, and therefore potentially fewer functional NMDA receptors, at the postsynaptic density. The associated decrease in PSD-95 protein at the postsynaptic density suggests that not only are glutamate receptors compromised in individuals with schizophrenia, but the overall spine architecture and downstream signaling supported by PSD-95 may also be deficient.
authors.affiliation: Schizophrenia Research Institute, Sydney, NSW, Australia; Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, NSW, Australia; School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Vibeke Sørensen
authors.initials: VS
authors.lastname: Catts
authors.affiliation: Schizophrenia Research Institute, Sydney, NSW, Australia; Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, NSW, Australia; School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Dominique Suzanne
authors.initials: DS
authors.lastname: Derminio
authors.affiliation: Department of Psychiatry, University of Pennsylvania , Philadelphia, PA, USA.
authors.forename: Chang-Gyu
authors.initials: CG
authors.lastname: Hahn
authors.affiliation: Schizophrenia Research Institute, Sydney, NSW, Australia; Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, NSW, Australia; School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Cynthia Shannon
authors.initials: CS
authors.lastname: Weickert