Quetiapine regulates neurogenesis in ischemic mice by inhibiting NF-κB p65/p50 expression

OBJECTIVES: Previously, we showed that quetiapine, an atypical antipsychotic drug, significantly attenuated neurodegeneration induced by global cerebral ischemia (GCI). The present work investigates the effects of quetiapine on neurogenesis. METHODS: Mice were treated with quetiapine (10 or 20 mg/kg/day; intraperitoneal injection) for 2 weeks and then subjected to GCI on day 15. Seven days after GCI, the mice were killed. Neuronal injury and neurogenesis were analysed using hematoxylin-eosin and 5-bromo-20-deoxyuridine stainings. Levels of nuclear factor kappaB (NF-kappaB) p65/p50 expressions were determined by immunohistochemistry and Western blot analysis. RESULTS: Global cerebral ischemia resulted in neuronal injury, neurogenesis and NF-kappaB p65/p50 expressions in hippocampus, especially in the dentate gyrus. Pre-administration of quetiapine significantly alleviated neuronal injury, while inhibiting neurogenesis and down-regulating NF-kappaB p65/p50 expression. DISCUSSION: NF-kappaB plays a key role in regulating neuron damage and neurogenesis. This work suggests that down-regulation of NF-kappaB expression may be one of the mechanisms by which quetiapine inhibits neurogenesis.