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Quetiapine facilitates oligodendrocyte development and prevents mice from myelin breakdown and behavioral changes

Molecular Psychiatry volume 13, pages 697–708 (2008)Cite this article

Abstract

Recent neuroimaging and postmortem studies have reported abnormalities in white matter of schizophrenic brains, suggesting the involvement of oligodendrocytes in the etiopathology of schizophrenia. This view is being supported by gene microarray studies showing the downregulation of genes related to oligodendrocyte function and myelination in schizophrenic brain compared to control subjects. However, there is currently little information available on the response of oligodendrocytes to antipsychotic drugs (APDs), which could be invaluable for corroborating the oligodendrocyte hypothesis. In this study we found: (1) quetiapine (QUE, an atypical APD) treatment in conjunction with addition of growth factors increased the proliferation of neural progenitors isolated from the cerebral cortex of embryonic rats; (2) QUE directed the differentiation of neural progenitors to oligodendrocyte lineage through extracellular signal-related kinases; (3) addition of QUE increased the synthesis of myelin basic protein and facilitated myelination in rat embryonic cortical aggregate cultures; (4) chronic administration of QUE to C57BL/6 mice prevented cortical demyelination and concomitant spatial working memory impairment induced by cuprizone, a neurotoxin. These findings suggest a new neural mechanism of antipsychotic action of QUE, and help to establish a role for oligodendrocytes in the etiopathology and treatment of schizophrenia.

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Acknowledgements

We are grateful to Gabriel Stegeman for her technical assistance. We thank Drs Sergey Fedoroff and Augusto Juorio for their helpful comments during the preparation of this manuscript. We also thank Dr Cheryl Corcoran for her editorial assistance. LX was supported by Canadian Psychiatric Research Foundation and Schizophrenia Society of Saskatchewan. YZ was supported by Saskatchewan Health Research Foundation.

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Author notes

  1. L Xiao

    Present address: 7Current address: Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, China.,

  2. L Xiao and H Xu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, Neuropsychiatry Research Unit, University of Saskatchewan, Saskatoon, SK, Canada

    L Xiao, Y Zhang, Z Wei, J He, W Jiang, L E Dyck & X M Li

  2. Department of Anatomy, School of Medicine, Southern Illinois University Carbondale, Carbondale, IL, USA

    H Xu

  3. Laboratory of Neuropharmacology, Wenzhou Medical College, Wenzhou, China

    X Li

  4. Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada

    R M Devon

  5. School of Life Science and Technology, Beijing Institute of Technology, Haidian, Beijing, China

    Y Deng

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Xiao, L., Xu, H., Zhang, Y. et al. Quetiapine facilitates oligodendrocyte development and prevents mice from myelin breakdown and behavioral changes. Mol Psychiatry 13, 697–708 (2008). https://doi.org/10.1038/sj.mp.4002064

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