quetiapine-fumarate and Carotid-Artery-Diseases

White matter impairment is a feature of vascular depression. The anti-psychotic quetiapine has been shown to enhance the therapeutic effects of anti-depressants on vascular depression, but the mechanism remains unknown. In this study, we found that 2 weeks of treatment with quetiapine prior to bilateral carotid artery occlusion and reperfusion, in an animal model of vascular depression, resulted in reduced myelin breakdown and oligodendrocyte loss compared to placebo-treated mice on post-operative day (POD) 7. For late stage of recovery (POD40), quetiapine treatment resulted in enhanced oligodendrocyte maturation relative to placebo. The results suggest that quetiapine is a potential intervention for oligodendrocyte damage and this may contribute to its anti-depressant effects through white matter protection in vascular depression.

Topics: Analysis of Variance; Animals; Antigens; Antipsychotic Agents; Brain Ischemia; Bromodeoxyuridine; Carotid Artery Diseases; Cell Differentiation; Dibenzothiazepines; Disease Models, Animal; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Hippocampus; Male; Mice; Myelin Basic Protein; Myelin Sheath; Oligodendroglia; Proteoglycans; Quetiapine Fumarate; Time Factors

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.

Topics: Animals; Carotid Arteries; Carotid Artery Diseases; Dibenzothiazepines; Hippocampus; Male; Maze Learning; Memory Disorders; Mice; Mice, Inbred ICR; Neurodegenerative Diseases; Quetiapine Fumarate; Staining and Labeling