Expression of oligodendrocyte-associated genes in dorsolateral prefrontal cortex of patients with schizophrenia.
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 (approximately 70 controls and approximately 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.
Mitkus
Shruti N
SN
Clinical Brain Disorders Branch, Section on Neuropathology, DIRP/NIMH/NIH, Bethesda, MD, 20892-1385, USA.
Hyde
Thomas M
TM
Vakkalanka
Radhakrishna
R
Kolachana
Bhaskar
B
Weinberger
Daniel R
DR
Kleinman
Joel E
JE
Lipska
Barbara K
BK
D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D035061:Control Groups; D005260:Female; D015870:Gene Expression / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009185:Myelin Proteins / Q000235:genetics* / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000378:metabolism*; D040081:Protein Array Analysis / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D012333:RNA, Messenger; C560487:MOBP protein, human; C571326:MOG protein, human; C405708:OLIG2 protein, human