Quetiapine mitigates the neuroinflammation and oligodendrocyte loss in the brain of C57BL/6 mouse following cuprizone exposure for one week

This study aimed at examining effects of quetiapine (QTP), an atypical antipsychotic, on the behaviors of mice which had consumed cuprizone (CPZ)-containing diet for one week and on inflammatory reactions and oligodendrocyte (OL) loss in brains of them. Young adult C57BL/6 mice, after fed CPZ-containing diet (0.2%, w/w) for one week, showed an increase in the locomotor activity in the open-field, and a decreased exploration time in the novel object recognition (NOR) test compared to controls. But, these changes were not seen in mice co-administered with QTP and CPZ. All mice in the four groups showed comparable performances in Y-maze test. After the behavioral tests, mice were killed and their brains were processed for immunohistochemical and immunofluorescence staining to examine OLs, astrocytes and microglia. The levels of proinflammatory cytokines TNF-alpha and IL-6 in certain brain regions were also evaluated by ELISA method. Mice in the NS+CPZ group showed fewer OLs, more activated astrocytes and microglia with higher immunofluorescence intensity in the examined brain regions of the corpus callosum, caudate putamen, cerebral cortex, and hippocampus. The levels of TNF-QTP and IL-6 in some of these brain regions were also increased. But these changes were completely blocked or effectively ameliorated in the QTP+CPZ group. These results demonstrated an anti-inflammatory effect of QTP in CPZ-exposed mice and this action may contribute to its protection on OLs and beneficial effects on the CPZ-induced behavioral changes in these mice. (C) 2015 Elsevier B.V. All rights reserved.