Quetiapine alleviates the cuprizone-induced white matter pathology in the brain of C57BL/6 mouse

Abstract

Recent human studies employing new magnetic resonance imaging techniques and micro-array analyses feature schizophrenia as a brain disease with alterations in white matter (WM), which is mainly composed of oligodendrocytes (OLs) and their processes wrapping around neuronal axons. To examine the putative role of OLs in the pathophysiology and treatment of schizophrenia, animal studies are essential. In the present study, C57BL/6 mice were given 0.2% cuprizone (CPZ) in their diet for five weeks during which they drank distilled water without or with quetiapine (QTP, 10 mg/kg). The mice fed with normal chow were used as controls. CPZ is a copper chelator and has been reported to induce consistent demyelination in the brain of C57BL/6 mouse by specifically damaging OLs. QTP is an atypical antipsychotic widely used in the treatment of schizophrenia and other psychotic disorders. In accordance with previous studies, CPZ-exposed mice showed pervasive myelin breakdown and demyelination. The amount of myelin basic protein (MBP) in the cerebral cortex was decreased by CPZ-exposure as shown in Western-blot analysis. In addition, the demyelinated sites were teemed with activated microglia and astrocytes but a few myelin forming OLs. Moreover, the activity of copper-zinc superoxide dismutase decreased in the cerebral cortex of CPZ-exposed mice. However, all of these pathological changes in WM were either prevented or alleviated in CPZ-exposed mice co-administered with QTP. These results suggest that the CPZ-exposed C57BL/6 mouse is a potential animal model to study possible roles of OLs in the pathogenesis and treatment of schizophrenia.