Presynaptic proteins in the prefrontal cortex of patients with schizophrenia and rats with abnormal prefrontal development

N. D. Halim, C. S. Weickert, B. W. McClintock, Thomas Hyde, Daniel Weinberger, Joel Kleinman, B. K. Lipska

Research output: Contribution to journalArticle

Abstract

Dysfunction of the prefrontal cortex in schizophrenia may be associated with abnormalities in synaptic structure and/or function and reflected in altered concentrations of proteins in presynaptic terminals and involved in synaptic plasticity (synaptobrevin/vesicle-associated membrane protein (VAMP), synaptosomal-associated protein-25 (SNAP-25), syntaxin, synaptophysin and growth-associated protein-43 (GAP-43)). We examined the immunoreactivity of these synapse-associated proteins via quantitative immunoblotting in the prefrontal cortex of patients with schizophrenia (n = 18) and in normal controls (n = 23). We also tested the stability of these proteins across successive post-mortem intervals in rat brains (at 0, 3, 12, 24, 48, and 70 h). To investigate whether experimental manipulation of prefrontal cortical development in the rat alters prefrontal synaptic protein levels, we lesioned the ventral hippocampus of rats on postnatal day 7 and measured immunoreactivity of presynaptic proteins in the prefrontal cortex on postnatal day 70. VAMP immunoreactivity was lower in the schizophrenic patients by 22% (P<0.03). There were no differences in the immunoreactivity of any other proteins measured in schizophrenic patients as compared to the matched controls. Proteins were fairly stable up to 24 h and thereafter the abundance of most proteins examined was significantly reduced (falling to as low as 20% of baseline levels at 48-70 h). VAMP immunoreactivity was higher in the lesioned rats as compared to sham controls by 22% (P<0.03). There were no significant differences between the lesioned rats and sham animals in any other presynaptic protein. These data suggest that apparently profound prefrontal cortical dysfunction in schizophrenia, as well as in an animal model of schizophrenia, may exist without gross changes in the abundance of many synaptic proteins but discrete changes in selected presynaptic molecules may be present.

Original languageEnglish (US)
Pages (from-to)797-810
Number of pages14
JournalMolecular Psychiatry
Volume8
Issue number9
DOIs
StatePublished - 2003
Externally publishedYes

Fingerprint

Prefrontal Cortex
Schizophrenia
R-SNARE Proteins
Proteins
Synaptosomal-Associated Protein 25
Qa-SNARE Proteins
GAP-43 Protein
Synaptophysin
Neuronal Plasticity
Protein Stability
Presynaptic Terminals
Immunoblotting
Synapses
Hippocampus
Animal Models
Brain

Keywords

  • Animal model
  • GAP-43
  • Hippocampus
  • SNAP-25
  • Synaptobrevin
  • Synaptophysin
  • Syntaxin
  • VAMP

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health

Cite this

Presynaptic proteins in the prefrontal cortex of patients with schizophrenia and rats with abnormal prefrontal development. / Halim, N. D.; Weickert, C. S.; McClintock, B. W.; Hyde, Thomas; Weinberger, Daniel; Kleinman, Joel; Lipska, B. K.

In: Molecular Psychiatry, Vol. 8, No. 9, 2003, p. 797-810.

Research output: Contribution to journalArticle

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