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Abstract #2521

MRI & Histological Evidence for the Blockade of Cuprizone-Induced Demyelination in C57/Bl6 Mice by Quetiapine

Prasant Chandran1, Jaymin Upadhyay1, Stella Markosyan2, Andrew Lisowski3, Wayne Buck3, Gerard B. Fox1, Mark Day1, Feng Luo1

1Translational Imaging & Biochemistry, Abbott Laboratories, Abbott Park, IL, United States; 2Neuroscience Discovery, Abbott Laboratories, Abbott Park, IL, United States; 3Cellular & Molecular Exploratory Toxicology, Abbott Laboratories, Abbott Park, IL, United States

Clinical neuroimaging studies have revealed that the schizophrenic brains exhibit oligodendrocytic white matter abnormalities. However, there is a lack of preclinical in vivo imaging assays addressing this issue. In the present study, mice fed with cuprizone mixed in diet exhibit myelin breakdown which was visualized using T2-weighted anatomical and Diffusion Tensor MR Imaging techniques. This was further confirmed by histological and immunohistochemistry staining methods. However, these pathological changes were prevented in cuprizone-exposed mice co-administered with quetiapine. These results suggest that the cuprizone-exposed mouse is a potential animal model to investigate the impact of treatments on white matter abnormalities in schizophrenia.