Expression of transcripts for myelination-related genes in the anterior cingulate cortex in schizophrenia.
Several recent studies have found changes in the expression of genes functionally related to myelination and oligodendrocyte homeostasis in schizophrenia. These studies utilized microarrays and quantitative PCR (QPCR), methodologies which do not permit direct, unamplified examination of mRNA expression. In addition, these studies generally only examined transcript expression in homogenates of gray matter. In the present study, we examined the expression of myelination-related genes previously implicated in schizophrenia by microarray or QPCR. Using in situ hybridization, we measured transcript expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), myelin-associated glycoprotein (MAG), transferrin (TF), quaking (QKI), gelsolin, myelin oligodendrocyte glycoprotein, v-erb-b2 erythroblastic leukemia viral oncogene homolog 3, erbb2 interacting protein, motility-related protein-1, SRY-box containing gene 10, oligodendrocyte transcription factor 2, peripheral myelin protein 22, and claudin-11 in both gray and white matter of the anterior cingulate cortex (ACC) in subjects with schizophrenia (n=41) and a comparison group (n=34). We found decreased expression of MAG, QKI, TF, and CNP transcripts in white matter. We did not find any differences in expression of these transcripts between medicated (n=31) and unmedicated (n=10) schizophrenics, suggesting that these changes are not secondary to treatment with antipsychotics. Finally, we found significant positive correlations between QKI and MAG or CNP mRNA expression, suggesting that the transcription factor QKI regulates MAG and CNP expression. Our results support the hypothesis that myelination and oligodendrocyte function are impaired in schizophrenia.
McCullumsmith
Robert E
RE
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA. smithrob@uab.edu
Gupta
Daya
D
Beneyto
Monica
M
Kreger
Emily
E
Haroutunian
Vahram
V
Davis
Kenneth L
KL
Meador-Woodruff
James H
JH
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000473:pathology; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D037102:Lectins; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics; D009185:Myelin Proteins / Q000235:genetics*; D018992:Myelin-Associated Glycoprotein; D009363:Neoplasm Proteins / Q000235:genetics; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*
D037102:Lectins; C115082:MAG protein, human; D018832:Molecular Chaperones; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D009363:Neoplasm Proteins; C490832:QKI protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors