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European Archives of Psychiatry and Clinical Neuroscience

Erschienen in:

01.03.2014 | Original Paper

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

verfasst von: Haiyun Xu, Hong-Ju Yang, Xin-Min Li

Erschienen in: European Archives of Psychiatry and Clinical Neuroscience | Ausgabe 2/2014

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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 developing OLs in the presence of CPZ. Oligodendrocyte progenitor cells (OPCs) were prepared from rat embryos; OLs at different developing 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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Titel: Differential effects of antipsychotics on the development of rat oligodendrocyte precursor cells exposed to cuprizone
verfasst von: Haiyun Xu
Hong-Ju Yang
Xin-Min Li
Publikationsdatum: 01.03.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: European Archives of Psychiatry and Clinical Neuroscience / Ausgabe 2/2014
Print ISSN: 0940-1334
Elektronische ISSN: 1433-8491
DOI: https://doi.org/10.1007/s00406-013-0414-3

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