Quetiapine regulates neurogenesis in ischemic mice by inhibiting NF-kappaB p65/p50 expression.
OBJECTIVE
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.


CONCLUSIONS
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.
Bi
Xiaoying
X
Department of Neurology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
Yan
Bin
B
Fang
Shaokuan
S
Yang
Yi
Y
He
Jue
J
Li
Xin-Min
XM
Kong
Jiming
J
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D003987:Dibenzothiazepines / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects*; D000069348:Quetiapine Fumarate; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism*
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA; D000069348:Quetiapine Fumarate; D001973:Bromodeoxyuridine