Quetiapine attenuates spatial memory impairment and hippocampal neurodegeneration induced by bilateral common carotid artery occlusion in mice

摘要

Quetiapine, a new atypical antipsychotic drug, has beneficial effects on cognitive impairment and neuropathological changes in treating chronic neurodegenerative diseases. Our previous studies have demonstrated that quetiapine may have neuroprotective properties. In the present study, we investigated the effects of a 2-week pre-administration of quetiapine (10 mg/kg/day, i.p.) on spatial memory impairment and hippocampal neurodegeneration induced by 60-minute bilateral common carotid artery occlusion (CCAO). Following a 7-day recovery phase from CCAO, the spatial memory of the mice was tested using a modified water maze test. After the behavioural test, the mice were sacrificed and brain sections were stained with NeuN (a neuron-specific soluble nuclear antigen), cresyl violet (Nissl), and Fluoro-Jade B. CCAO significantly induced spatial memory impairment and caused neurodegeneration in the hilus of hippocampus, while quetiapine significantly attenuated these changes. This is the first study showing that quetiapine significantly attenuates CCAO-induced spatial memory impairment and this improvement parallels the alleviative effects of quetiapine on CCAO-induced neurodegeneration in the hilus of hippocampus. The results suggest that quetiapine may have defending effects on the impairments induced by cerebral ischemia, which enhances our understanding about the mechanisms of quetiapine. (c) 2007 Elsevier Inc. All rights reserved.