Neurodegeneration, Neuroprotection, and Disease-Oriented NeuroscienceResearch PaperMagnetic resonance imaging and histological evidence for the blockade of cuprizone-induced demyelination in C57BL/6 mice

Several neuroimaging studies have revealed that the brains of schizophrenic patients exhibit abnormalities in white matter pathways. Using magnetic resonance imaging (MRI) methods, such as T2-weighted imaging and diffusion tensor imaging (DTI), it is possible to objectively quantify white matter structural properties in patients as well as the pharmacological effect on white matter. In the preclinical domain, these strategies, however, have been hindered by a lack of in vivo imaging assays. One preclinical approach that has been used to pharmacologically challenge the integrity of the white matter is the chronic administration of the copper chelator, cuprizone. In the present study, C57BL/6 mice were given 0.2% cuprizone in their diet for five weeks with or without the antipsychotic drug, quetiapine (10 mg/kg). In accordance with previous studies, myelin breakdown in cuprizone-exposed mice was measured by using T2-weighted MRI and DTI. Here, we demonstrate that cuprizone-induced white matter changes were attenuated by quetiapine treatment. These MRI-based results and trends were confirmed by histological and immunohistochemistry measures. This study suggests that the cuprizone-exposed C57BL/6 mouse is a potential animal model to investigate the impact of treatments on white matter abnormalities in schizophrenia.

▶Using DTI as a translatable pre-clinical imaging biomarker. ▶Validation of a mouse model of white matter demyelination using T2 and DTI. ▶Cuprizone-induced demyelination blocked by an atypical antipsychotic, quetiapine. ▶Translational imaging biomarker approach for novel schizophrenia therapies.