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Differential effects of antipsychotics on the development of rat oligodendrocyte precursor cells exposed to cuprizone

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Abstract

Cuprizone (CPZ) is a copper-chelating agent and has been shown to induce white matter damage in mice and rats. The compromised white matter and oligodendrocytes (OLs) respond to some antipsychotics in vivo. However, little is known about the effects of antipsychotics on cultured OLs in the presence of CPZ. The aim of this study was to examine effects of some antipsychotics on develo** OLs in the presence of CPZ. Oligodendrocyte progenitor cells (OPCs) were prepared from rat embryos; OLs at different develo** stages were labeled with specific antibodies; levels of CNP and MBP proteins in mature OLs were assessed by Western-blot analysis; malondialdehyde (MDA) levels and activity of catalase were evaluated as well for an assessment of oxidative stress and antioxidative status. In immunofluorescent staining, CPZ was shown to inhibit the differentiation of cultured OPCs into O4-positive cells, reduce the maturation of O4-positive cells into CNP- and MBP-positive cells, and decrease levels of CNP and MBP in mature OLs. These inhibitory effects of CPZ were ameliorated by clozapine and quetiapine (QUE), but not by haloperidol and olanzapine. Further experiments were performed to explore the mechanism of the protective effects of QUE. QUE attenuated the decreases in CNP and MBP in CPZ-treated OLs, and blocked the CPZ-induced increase in MDA and decrease in catalase activity in cultured OLs. These results are relevant to the pathophysiology and treatment of schizophrenia considering the aberrant white matter development and evidence suggesting the derangement of the oxidant and antioxidant defense system in some of the patients with schizophrenia.

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Acknowledgments

This work was supported by grants from Southern Illinois University Carbondale (Haiyun Xu) and the University of Manitoba (Haiyun Xu and **n-Min Li).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Mental Health Center, Shantou University Medical College, Shantou, People’s Republic of China

    Haiyun Xu

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

    Haiyun Xu & Hong-Ju Yang

  3. Department of Psychiatry, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada

    **n-Min Li

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  1. Haiyun Xu
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  2. Hong-Ju Yang
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Correspondence to Haiyun Xu.

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Xu, H., Yang, HJ. & Li, XM. Differential effects of antipsychotics on the development of rat oligodendrocyte precursor cells exposed to cuprizone. Eur Arch Psychiatry Clin Neurosci 264, 121–129 (2014). https://doi.org/10.1007/s00406-013-0414-3

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  • DOI: https://doi.org/10.1007/s00406-013-0414-3

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