4.4 Article

Expression of oligodendrocyte-associated genes in dorsolateral prefrontal cortex of patients with schizophrenia

Journal

SCHIZOPHRENIA RESEARCH
Volume 98, Issue 1-3, Pages 129-138

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.schres.2007.09.032

Keywords

schizophrenia; myelin; oligodendrocytes; MOBP; CNP; OLIG2; postmortem studies

Categories

Funding

  1. NATIONAL INSTITUTE OF MENTAL HEALTH [ZIAMH002399, ZICMH002908, ZICMH002903] Funding Source: NIH RePORTER
  2. Intramural NIH HHS [Z99 MH999999, Z01 MH002399-18] Funding Source: Medline

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Prior studies have found decreased mRNA expression of oligodendrocyte-associated genes in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia. However, it is unclear which specific genes are affected and whether the changes occur in the cortical white or grey matter. We assessed the mRNA expression levels of four oligodendrocyte-related genes: myelin-associated basic protein (MOBP), myelin-associated glycoprotein (MAG), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and oligodendrocyte-lineage transcription factor 2 (OLIG2) in DLPFC white and grey matter using quantitative-PCR (similar to 70 controls and similar to 30 patients with schizophrenia). We also examined the effects of high-risk polymorphisms in CNP and OLIG2 on mRNA levels of these genes. We found that genetic polymorphisms in CNP (rs2070106) and OLIG2 (rs1059004 and rs9653711), previously associated with schizophrenia, predicted low expression of these genes. Expression of MAG, CNP and OLIG2 did not differ between patients with schizophrenia and controls in the grey or white matter but MOBP mRNA levels were increased in the DLPFC white matter in patients with a history of substance abuse. MOBP and CNP protein in the white matter was not altered. Although previously reported reductions in the expression of myelin-related genes in the DLPFC were not detected, we show that individuals carrying risk-associated alleles in oligodendrocyte-related genes had relatively lower transcript levels. These data illustrate the importance of genetic background in gene expression studies in schizophrenia. Published by Elsevier B.V.

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