摘要
目的前期证明胍丁胺（agmatlne，Agm）作为一种新型神经递质具有抗抑郁作用，能够促进慢性应激小鼠海马神经元再生。本实验通过观察胍丁胺对体外培养海马神经前体细胞增殖的影响及作用机制，探讨其抗抑郁作用的细胞分子机制。方法培养扩增新生大鼠海马神经前体细胞，通过3H-TdR参入法和CCK-8试剂盒检测胍丁胺对其增殖的影响；培养体系内加入H89（PKA特异性抑制剂）或PD98059（MEK特异性抑制剂），观察这两种抑制剂对胍丁胺作用的影响。结果胍丁胺在0．1-10μmol．L^-1浓度范围内，浓度依赖性地促进神经前体细胞的增殖，这种促增殖作用可以被H89（10μmol·L^-1）和PD98059（10μmol．L^-1）取消。结论胍丁胺可以促进体外培养的海马神经前体细胞增殖，此作用与cAMP-PKA-CREB通路和MEK-ERK-CREB通路相关。
Aim Agmatine had been proved to have antidepressant-like effect with up-regulated hippocam- pal neurogenesis in chronically stressed mice as a novel neurotransmitter in the mammalian brain. In the present study, the effect of agmatine on the proliferation of neural progenitor cells （NPCs） from hippocampus was investigated to clarify the cellular mechanisms of agmatine’s antidepressant-like effect in vitro. Methods NPCs from hippocampus of neonatal rats were isolated and cultured, the action of agmatine, H89 （ PKA inhibitor） and PD98059 （MEK inhibitor） on NPCs proliferation were observed using 3H-thymidine incorpora-tion assay and CCK-8 kit assay. Resets Treatment with agmatine（0. 1 - 10 μmol.L^-1 ） significantly increased the proliferation of cultured hippocampal progenitor cells in a dose-dependent manner, and this action was fully prevented by H89 （ 10μmol.L^-1 ） or PD98059（ 10 μmol.L^-1）. Conclusion It was deduced that agmatine increased proliferation of hippocampal progenitor cells in vitro and this effect was mediated through cAMP-PKA-CREB and MEK-ERK- CREB pathways.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2008年第5期583-587,共5页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No30400600
No30472018)
国家高技术研究发展计划(863计划)资助项目(No2007AA02Z400)
国家重点基础研究发展计划(973计划)资助项目(No2007CB512307)
博士后科学基金资助项目(No2005038332)
关键词
胍丁胺
抑郁
神经前体细胞
信号通路
agmatine
depression
neural progenitorcells
signaling pathways
