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Microarray Database Mining and Cell Differentiation Defects in Schizophrenia

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Book cover Software Tools and Algorithms for Biological Systems

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 696))

Abstract

The causes of schizophrenia remain unknown, but a key role of oligodendrocytes and of the myelination process carried out by them has gained increasing support. The adult human brain parenchyma contains a relatively large population of progenitor cells that can generate oligodendrocytes. Defects in these adult oligodendrocyte progenitor cells (OPCs) or in their proliferation/differentiation have received little attention as potential causes of schizophrenia yet. We compared the set of genes whose expression is modified in schizophrenia, as revealed by our microarray studies, with genes specifically expressed in stem cells, as revealed by studies on human embryonic stem cells. We also evaluated the genes that are upregulated when stem cells engage in differentiation programs. These genes can be viewed as fingerprints or signatures for differentiation processes. The comparisons revealed that a substantial fraction of the genes downregulated in the brains of persons with schizophrenia belong to the differentiation signature. A plausible interpretation of our observations is that a cell differentiation process, possibly of adult OPCs to oligodendrocytes, is perturbed in schizophrenia. These observations constitute an incentive for a new direction of study, aimed at investigating the potential role of OPCs in schizophrenia.

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References

  1. Hakak Y, Walker JR, Li C et al (2001) Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci USA 98: 4746–4751.

    Article  PubMed  CAS  Google Scholar 

  2. Davis KL, Haroutunian V (2003) Global expression-profiling studies and oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet 362: 758.

    Article  PubMed  Google Scholar 

  3. Dracheva S, Davis KL, Chin B et al (2006) Myelin-associated mRNA and protein expression deficits in the anterior cingulate cortex and hippocampus in elderly schizophrenia patients. Neurobiol Dis 21: 531–540.

    Article  PubMed  CAS  Google Scholar 

  4. Katsel P, Davis KL, Haroutunian V (2005) Variations in myelin and oligodendrocyte-related gene expression across multiple brain regions in schizophrenia: a gene ontology study. Schizophr Res 79: 157–173.

    Article  PubMed  Google Scholar 

  5. Katsel P, Davis KL, Haroutunian V (2004) Large-scale microarray studies of gene expression in multiple regions of the brain in schizophrenia and Alzheimers disease. Int Rev Neurobiol 63: 41–81.

    Article  Google Scholar 

  6. McCullumsmith RE, Gupta D, Beneyto M et al (2007) Expression of transcripts for myelination-related genes in the anterior cingulate cortex in schizophrenia. Schizophr Res 90(1–3): 15–27.

    Article  PubMed  Google Scholar 

  7. Barley K, Dracheva S, Byne W (2009) Subcortical oligodendrocyte- and astrocyte-associated gene expression in subjects with schizophrenia, major depression and bipolar disorder. Schizophr Res 112(1–3): 54–64.

    Article  PubMed  Google Scholar 

  8. Tkachev D, Mimmack ML, Huffaker SJ et al (2007) Further evidence for altered myelin biosynthesis and glutamatergic dysfunction in schizophrenia. Int J Neuropsychopharmacol 10(4): 557–63.

    Article  PubMed  CAS  Google Scholar 

  9. Aston C, Jiang L, Sokolov BP (2004) Microarray analysis of postmortem temporal cortex from patients with schizophrenia. J Neurosci Res 77: 858–866.

    Article  PubMed  CAS  Google Scholar 

  10. Aberg K, Saetre P, Jareborg N et al (2006) Human QKI, a potential regulator of mRNA expression of human oligodendrocyte-related genes involved in schizophrenia. Proc Natl Acad Sci USA 103: 7482–7487.

    Article  PubMed  Google Scholar 

  11. Iwamoto K, Bundo M, Yamada K et al (2005) DNA methylation status of SOX10 correlates with its downregulation and oligodendrocyte dysfunction in schizophrenia. J Neurosci 5: 5376–5381.

    Article  Google Scholar 

  12. Sugai T, Kawamura M, Iritani S et al (2004) Prefrontal abnormality of schizophrenia revealed by DNA microarray Impact on glial and neurotrophic gene expression. Ann NY Acad Sci 1025: 84–91.

    Article  PubMed  CAS  Google Scholar 

  13. Flynn SW, Lang DJ, MacKay AL et al (2003) Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins. Mol Psychiatry 8: 811–820.

    Article  PubMed  CAS  Google Scholar 

  14. Liu Y, Rao M (2004) Glial progenitors in the CNS and possible lineage relationships among them. Biol Cell 96: 279–290.

    Article  PubMed  CAS  Google Scholar 

  15. Polito A, Reynolds R (2005) NG2-expressing cells as oligodendrocyte progenitors in the normal and demyelinated adult central nervous system. J Anat 207: 707–716.

    Article  PubMed  Google Scholar 

  16. Nunes MC, Roy NS, Keyoung HM et al (2003) Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med 9: 439–447.

    Article  PubMed  CAS  Google Scholar 

  17. Nishiyama A, Watanabe M, Yang Z et al (2002) Identity, distribution, and development of polydendrocytes: NG2-expressing glial cells. J Neurocytol 31: 437–445.

    Article  PubMed  CAS  Google Scholar 

  18. Ruffini F, Arbour N, Blain M et al (2004) Distinctive properties of human adult brain-derived myelin progenitor cells. Am J Pathol 165: 2167–2175.

    Article  PubMed  Google Scholar 

  19. Windrem MS, Nunes MC, Rashbaum WK et al. (2004) Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. Nat Med 10: 93–97.

    Article  PubMed  CAS  Google Scholar 

  20. Dawson MR, Polito A, Levine JM et al (2003) NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS. Mol Cell Neurosci 24: 476–488.

    Article  PubMed  CAS  Google Scholar 

  21. Suárez-Fariñas M, Noggle S, Heke M et al (2005) Comparing independent microarray studies: the case of human embryonic stem cells. BMC Genomics 6: 99.

    Article  PubMed  Google Scholar 

  22. Haroutunian V, Katsel P, Dracheva S et al (2006) The human homolog of QK1 gene affected in the severe dysmyelination “quaking” mouse phenotype is downregulated in multiple brain regions in schizophrenia. Am J Psychiatry 163: 1–3.

    Article  Google Scholar 

  23. Kessaris N, Pringle N, Richardson WD (2001) Ventral neurogenesis and the neuron-glial switch. Neuron 31: 677–680.

    Article  PubMed  CAS  Google Scholar 

  24. Stolt CC, Rehberg S, Ader M et al (2002) Terminal differentiation of myelin-forming oligodendrocytes depends on the transcription factor Sox10. Genes Dev 16: 165–170.

    Article  PubMed  CAS  Google Scholar 

  25. Georgieva L, Moskvina V, Peirce T et al (2006) Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2) and interacting genes influence susceptibility to schizophrenia. Proc Natl Acad Sci USA 103: 12469–12474.

    Article  PubMed  CAS  Google Scholar 

  26. Harrison PJ, Weinberger DR (2005) Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 10: 40–68.

    Article  PubMed  CAS  Google Scholar 

  27. Rapoport JL, Addington AM, Frangou S et al (2005) The neurodevelopmental model of schizophrenia: update. Mol Psychiatry 10: 434–449.

    Article  PubMed  CAS  Google Scholar 

  28. Hof PR, Haroutunian V, Friedrich VL Jr et al (2003) Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia. Biol Psychiatry 53: 1075–1085.

    Article  PubMed  CAS  Google Scholar 

  29. Uranova NA, Vostrikov VM, Orlovskaya DD et al (2004) Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium. Schizophr Res 67: 269–275.

    Article  PubMed  Google Scholar 

  30. Reif A, Fritzen S, Finger M, Strobel A et al (2006) Neural stem cell proliferation is decreased in schizophrenia, but not in depression. Mol Psychiatry 11: 514–522.

    Article  PubMed  CAS  Google Scholar 

  31. Menn B, Garcia-Verdugo JM, Yaschine C et al (2006) Origin of oligodendrocytes in the subventricular zone of the adult brain. J Neurosci 26: 7907–7918.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank Drs Mayte Suárez-Fariñas and Marcelo Magnasco from the Rockefeller University for sharing data, critical reading of the manuscript, and evaluation of the computational/statistical aspects, and Dr Gregory Elder from the Mount Sinai School of Medicine for suggestions and comments. This research was funded by MH45212 (KLD), MH064673 and VA-MIRECC (VH). The generation of the microarray data used here was supported in part by research sponsored by Gene Logic Inc. (Gaithersburg, MD).

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Authors and Affiliations

  1. Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY, 10029, USA

    Aurelian Radu

Authors
  1. Aurelian Radu
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  2. Gabriela Hristescu
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  3. Pavel Katsel
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  4. Vahram Haroutunian
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  5. Kenneth L. Davis
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Corresponding author

Correspondence to Aurelian Radu .

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Editors and Affiliations

  1. Dept. Computer Science, University of Georgia, Athens, 30602-7404, Georgia, USA

    Hamid R. Arabnia

  2. , Department of Computer Science, Lamar University, Beaumont, 77710, Texas, USA

    Quoc-Nam Tran

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Radu, A., Hristescu, G., Katsel, P., Haroutunian, V., Davis, K.L. (2011). Microarray Database Mining and Cell Differentiation Defects in Schizophrenia. In: Arabnia, H., Tran, QN. (eds) Software Tools and Algorithms for Biological Systems. Advances in Experimental Medicine and Biology, vol 696. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7046-6_7

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