Expression of Oligodendrocyte-associated Genes in Dorsolateral Prefrontal Cortex of Patients with Schizophrenia

Overview

Journal Schizophr Res

Specialty Psychiatry

Date 2007 Oct 30

PMID 17964117

Citations 55

Authors

Shruti N Mitkus

Thomas M Hyde

Radhakrishna Vakkalanka

Bhaskar Kolachana

Daniel R Weinberger

Joel E Kleinman

Barbara K Lipska

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Single-Cell Sequencing in Neurodegenerative Disorders.

Pozojevic J, Spielmann M Mol Diagn Ther. 2023; 27(5):553-561.

PMID: 37552451 PMC: 10435411. DOI: 10.1007/s40291-023-00668-9.

Disturbed Oligodendroglial Maturation Causes Cognitive Dysfunction in Schizophrenia: A New Hypothesis.

Falkai P, Rossner M, Raabe F, Wagner E, Keeser D, Maurus I Schizophr Bull. 2023; 49(6):1614-1624.

PMID: 37163675 PMC: 10686333. DOI: 10.1093/schbul/sbad065.

Elevated endogenous GDNF induces altered dopamine signalling in mice and correlates with clinical severity in schizophrenia.

Matlik K, Garton D, Montano-Rodriguez A, Olfat S, Eren F, Casserly L Mol Psychiatry. 2022; 27(8):3247-3261.

PMID: 35618883 PMC: 9708553. DOI: 10.1038/s41380-022-01554-2.

Abnormal oligodendrocyte function in schizophrenia explains the long latent interval in some patients.

Fessel J Transl Psychiatry. 2022; 12(1):120.

PMID: 35338111 PMC: 8956594. DOI: 10.1038/s41398-022-01879-0.

Single-cell sequencing of human midbrain reveals glial activation and a Parkinson-specific neuronal state.

Smajic S, Prada-Medina C, Landoulsi Z, Ghelfi J, Delcambre S, Dietrich C Brain. 2021; 145(3):964-978.

PMID: 34919646 PMC: 9050543. DOI: 10.1093/brain/awab446.

References

Zai G, King N, Wigg K, Couto J, Wong G, Honer W . Genetic study of the myelin oligodendrocyte glycoprotein (MOG) gene in schizophrenia. Genes Brain Behav. 2005; 4(1):2-9. DOI: 10.1111/j.1601-183X.2004.00089.x. View

Narayan S, Kass K, Thomas E . Chronic haloperidol treatment results in a decrease in the expression of myelin/oligodendrocyte-related genes in the mouse brain. J Neurosci Res. 2006; 85(4):757-65. DOI: 10.1002/jnr.21161. View

Prabakaran S, Swatton J, Ryan M, Huffaker S, Huang J, Griffin J . Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry. 2004; 9(7):684-97, 643. DOI: 10.1038/sj.mp.4001511. View

Aston C, Jiang L, Sokolov B . Microarray analysis of postmortem temporal cortex from patients with schizophrenia. J Neurosci Res. 2004; 77(6):858-66. DOI: 10.1002/jnr.20208. View

Liu J, Lewohl J, Dodd P, Randall P, Harris R, Mayfield R . Gene expression profiling of individual cases reveals consistent transcriptional changes in alcoholic human brain. J Neurochem. 2004; 90(5):1050-8. DOI: 10.1111/j.1471-4159.2004.02570.x. View

Covault J, Lee J, Jensen K, Kranzler H . Nogo 3'-untranslated region CAA insertion: failure to replicate association with schizophrenia and demonstration of marked population difference in frequency of the insertion. Brain Res Mol Brain Res. 2004; 120(2):197-200. DOI: 10.1016/j.molbrainres.2003.11.001. View

Thompson P, Hayashi K, Simon S, Geaga J, Hong M, Sui Y . Structural abnormalities in the brains of human subjects who use methamphetamine. J Neurosci. 2004; 24(26):6028-36. PMC: 6729247. DOI: 10.1523/JNEUROSCI.0713-04.2004. View

Xiong L, Rouleau G, DeLisi L, St-Onge J, Najafee R, Riviere J . CAA insertion polymorphism in the 3'UTR of Nogo gene on 2p14 is not associated with schizophrenia. Brain Res Mol Brain Res. 2005; 133(1):153-6. DOI: 10.1016/j.molbrainres.2004.08.024. View

Dracheva S, Davis K, Chin B, Woo D, Schmeidler J, Haroutunian V . Myelin-associated mRNA and protein expression deficits in the anterior cingulate cortex and hippocampus in elderly schizophrenia patients. Neurobiol Dis. 2005; 21(3):531-40. DOI: 10.1016/j.nbd.2005.08.012. View

10.

Watanabe Y, Fukui N, Nunokawa A, Muratake T, Kaneko N, Kitamura H . No association between the ERBB3 gene and schizophrenia in a Japanese population. Neurosci Res. 2007; 57(4):574-8. DOI: 10.1016/j.neures.2007.01.001. View

11.

Dwork A, Mancevski B, Rosoklija G . White matter and cognitive function in schizophrenia. Int J Neuropsychopharmacol. 2007; 10(4):513-36. DOI: 10.1017/S1461145707007638. View

12.

McCullumsmith R, Gupta D, Beneyto M, Kreger E, Haroutunian V, Davis K . Expression of transcripts for myelination-related genes in the anterior cingulate cortex in schizophrenia. Schizophr Res. 2007; 90(1-3):15-27. PMC: 1880890. DOI: 10.1016/j.schres.2006.11.017. View

13.

Wan C, Yang Y, Feng G, Gu N, Liu H, Zhu S . Polymorphisms of myelin-associated glycoprotein gene are associated with schizophrenia in the Chinese Han population. Neurosci Lett. 2005; 388(3):126-31. DOI: 10.1016/j.neulet.2005.06.051. View

14.

McInnes L, Lauriat T . RNA metabolism and dysmyelination in schizophrenia. Neurosci Biobehav Rev. 2006; 30(4):551-61. DOI: 10.1016/j.neubiorev.2005.10.003. View

15.

Nackley A, Shabalina S, Tchivileva I, Satterfield K, Korchynskyi O, Makarov S . Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science. 2006; 314(5807):1930-3. DOI: 10.1126/science.1131262. View

16.

Usui H, Takahashi N, Saito S, Ishihara R, Aoyama N, Ikeda M . The 2',3'-cyclic nucleotide 3'-phosphodiesterase and oligodendrocyte lineage transcription factor 2 genes do not appear to be associated with schizophrenia in the Japanese population. Schizophr Res. 2006; 88(1-3):245-50. DOI: 10.1016/j.schres.2006.07.019. View

17.

Qin W, Gao J, Xing Q, Yang J, Qian X, Li X . A family-based association study of PLP1 and schizophrenia. Neurosci Lett. 2005; 375(3):207-10. DOI: 10.1016/j.neulet.2004.11.013. View

18.

Tan E, Chong S, Wang H, Lim E, Teo Y . Gender-specific association of insertion/deletion polymorphisms in the nogo gene and chronic schizophrenia. Brain Res Mol Brain Res. 2005; 139(2):212-6. DOI: 10.1016/j.molbrainres.2005.05.010. View

19.

Albertson D, Pruetz B, Schmidt C, Kuhn D, Kapatos G, Bannon M . Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004; 88(5):1211-9. PMC: 2215309. DOI: 10.1046/j.1471-4159.2003.02247.x. View

20.

Hof P, Haroutunian V, Friedrich Jr V, Byne W, Buitron C, Perl D . Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia. Biol Psychiatry. 2003; 53(12):1075-85. DOI: 10.1016/s0006-3223(03)00237-3. View