TY - JOUR
T1 - Expression of transcripts for myelination-related genes in the anterior cingulate cortex in schizophrenia
AU - McCullumsmith, Robert E.
AU - Gupta, Daya
AU - Beneyto, Monica
AU - Kreger, Emily
AU - Haroutunian, Vahram
AU - Davis, Kenneth L.
AU - Meador-Woodruff, James H.
PY - 2007/2
Y1 - 2007/2
N2 - 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.
AB - 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.
KW - Human
KW - In situ hybridization
KW - Myelin
KW - Oligodendrocyte
KW - Postmortem
UR - http://www.scopus.com/inward/record.url?scp=33846645320&partnerID=8YFLogxK
U2 - 10.1016/j.schres.2006.11.017
DO - 10.1016/j.schres.2006.11.017
M3 - Article
C2 - 17223013
AN - SCOPUS:33846645320
SN - 0920-9964
VL - 90
SP - 15
EP - 27
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 1-3
ER -