Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia

R. Hashimoto, R. E. Straub, C. S. Weickert, T. M. Hyde, J. E. Kleinman, D. R. Weinberger

Research output: Contribution to journalArticle

Abstract

Genetic linkage and association have implicated neuregulin-1 (NRG-1) as a schizophrenia susceptibility gene. We measured mRNA expression levels of the three major isoforms of NRG-1 (ie type I, type II, and type III) in the postmortem dorsolateral prefrontal cortex (DLPFC) from matched patients and controls using real-time quantitative RT-PCR. Expression levels of three internal controls - GAPDH, cyclophilin, and β-actin - were unchanged in schizophrenia, and there were no changes in the absolute levels of the NRG-1 isoforms. However, type I expression normalized by GAPDH levels was significantly increased in schizophrenia DLPFC (by 23%) and positively correlated with antipsychotic medication dosage. Type II/type I and type II/type III ratios were significantly decreased (18 and 23% respectively). There was no effect on the NRG-1 mRNA levels of genotype at two SNPs previously associated with schizophrenia, suggesting that these alleles are not functionally responsible for abnormal NRG-1 expression patterns in patients. Subtle abnormalities in the expression patterns of NRG-1 mRNA isoforms in DLPFC may be associated with schizophrenia.

Original languageEnglish (US)
Pages (from-to)299-307
Number of pages9
JournalMolecular psychiatry
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2004
Externally publishedYes

Keywords

  • Dorsolateral prefrontal cortex
  • Expression
  • Isoform
  • Neuregulin-1
  • Postmortem brain
  • Schizophrenia

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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