Notch信号通路在非典型抗精神病药物调节海马神经发生中的作用

抗精神病药物是治疗精神分裂症的主要手段，然而目前对于非典型抗精神病药物（SGA）作用机制研究的工作还不完整。文献及我们过去的工作证明，此类药物有促神经发生的作用，但其分子机制还不清楚。Notch是调节神经发生的重要信号通路，我们前期研究发现SGA药物在改善大鼠海马神经发生的同时，亦能上调Notch相关分子Notch1和Hes1的水平。我们推测，Notch 信号通路是非典型抗精神病药物调节海马神经发生中的关键通路。为进一步验证该假说,本研究拟以精神分裂样小鼠模型、RBP-J（Notch 信号关键转录因子）基因剔除小鼠和神经干细胞为研究工具，观察Notch信号通路在SGA调节神经发生过程中的作用，为抗精神病药物作用机理和新药研发提供新思路和实验依据。

Antipsychotic is the main therapeutic method to schizophrenia, but the mechanism of second-generation antipsychotic (SGA) is still incomplete. Literatures and our previous studies showed that SGA could elevate the neurogenesis of brain, but the molecular mechanism is unclear. Notch signaling play an important role in the regulation of neurogenesis, our recent work found that beside the up-regulation of the hippocampal neurogenesis, SGA also elevated the expression levels of Notch1 and Hes1, the correlated molecules of Notch signaling. We hypothesized that Notch signaling might play a key role in the hippocampal neurogenesis that promoted by SGA. In the present study, we use the mouse model of schizophrenia, RBP-J (key transcriptional factor of Notch signaling) gene knock-out mice and neural stem cell to investigate the relationship between the up-regulation of neurogenesis of SGA and Notch signaling.Thus, we hope to shed light on more detailed understanding the role of Notch signaling in the regulation of neurogenesis of SGA and provide a newly target and thinking for the research and development of new drugs and pathological study of schizophrenia.