Heat shock protein 12A shows reduced expression in the prefrontal cortex of subjects with schizophrenia

Julie L. Pongrac, Frank A. Middleton, Lansha Peng, David A. Lewis, Pat Levitt, Károly Mirnics

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Deoxyribonucleic acid microarray analyses of dorsolateral prefrontal cortex (DLPFC) area 9 from 10 matched pairs of schizophrenic and control subjects revealed a consistent and significant decrease (p =. 001; mean log2 signal difference = -.58) in transcript expression for a gene clone KIAA0417. This database entry has been recently annotated as two highly homologous members of a heat-shock protein family (HSPA12A and HSPA12B). We followed up our initial results by in situ hybridization in subjects with schizophrenia, major depression, and a chronic haloperidol-treated nonhuman primate model. Furthermore, we investigated the distribution of HSPA12A and HSPA12B transcripts across the human and nonhuman primate brain. We found that HSPA12A (but not HSPA12B) is highly expressed in the human brain and shows a neuron- and region-specific transcript distribution, with strongest expression in the frontal and occipital cortical regions. HSPA12A messenger ribonucleic acid was significantly reduced (p <. 01; mean log2 optical density difference = -.84) across subjects with schizophrenia but not in the DLPFC of subjects with major depression or in monkeys chronically treated with haloperidol. The data are consistent with metabolic alterations in schizophrenia, reflected in selective changes in the expression of certain genes encoding proteins involved in cellular metabolism or metabolic responsiveness.

Original languageEnglish (US)
Pages (from-to)943-950
Number of pages8
JournalBiological Psychiatry
Volume56
Issue number12
DOIs
StatePublished - Dec 15 2004

Keywords

  • Microarray
  • chaperone
  • gene expression
  • haloperidol
  • in situ hybridization
  • postmortem

ASJC Scopus subject areas

  • Biological Psychiatry

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