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.