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 kappa B (NF-kappa B) p65/p50 expressions were determined by immunohistochemistry and Western blot analysis. Results: Global cerebral ischemia resulted in neuronal injury, neurogenesis and NF-kappa B p65/p50 expressions in hippocampus, especially in the dentate gyrus. Pre-administration of quetiapine significantly alleviated neuronal injury, while inhibiting neurogenesis and down-regulating NFkB p65/p50 expression. Discussion: NF-kappa B plays a key role in regulating neuron damage and neurogenesis. This work suggests that down-regulation of NF-kappa B expression may be one of the mechanisms by which quetiapine inhibits neurogenesis. [Neurol Res 2009; 31: 159-166]