Moclobemide up-regulates proliferation of hippocarnpal progenitor cells in chronically stressed mice  

作　　者：Yun-fengLI You-zhiZHANG Yan-qinLIU Heng-linWANG LiYUAN Zhi-puLUO 

机构地区：[1]BeijingInstituteofPharmacologyandToxicology,Beijing100850 [2]DepartmentofAnesthesiology,309HospitalofBeijing,Beijing100091,China

出　　处：《Acta Pharmacologica Sinica》2004年第11期1408-1412,共5页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China(No30300419)Natural Science Foundation of Beijing City(No7042052).

摘　　要：AIM: To explore the action mechanism of antidepressants. METHODS: The PC12 cell proliferation was detected by flow cytometry,. The proliferation of hippocampal progenitor cells and level of brain-derived neurotrophic factor (BDNF) were measured by immunohistochemistry. RESULTS: Treatment with N-methylaspartate (NMDA) 600μmol/L for 3 d significantly decreased the percentage of S-phase in PC12 cells, while in the presence of classical antidepressant, moclobemide (MOC) 2 and 10μmol/L, the percentage in S-phase increased. Furthermore, the proliferation of progenitor cells in hippocampal dentate gyrus (subgranular zone), as well as the level of BDNF in hippocampus significantly decreased in chronically stressed mice, while chronic administration with MOC 40 mg/kg (ip) up-regulated the progenitor cell proliferation and BDNF level in the same time course. CONLUSION: Up-regulation of the proliferation of hippocampal progenitor cells is one of the action mechanisms for MOC, which may be closely related to the elevation of BDNF level at the same time. These results also extend evidence for our hypothesis that up-regulation of the hippocampal neurogenesis is one of the common mechanisms for antidepressants.AIM: To explore the action mechanism of antidepressants. METHODS: The PC12 cell proliferation was detected by flow cytometry,. The proliferation of hippocampal progenitor cells and level of brain-derived neurotrophic factor (BDNF) were measured by immunohistochemistry. RESULTS: Treatment with N-methylaspartate (NMDA) 600μmol/L for 3 d significantly decreased the percentage of S-phase in PC12 cells, while in the presence of classical antidepressant, moclobemide (MOC) 2 and 10μmol/L, the percentage in S-phase increased. Furthermore, the proliferation of progenitor cells in hippocampal dentate gyrus (subgranular zone), as well as the level of BDNF in hippocampus significantly decreased in chronically stressed mice, while chronic administration with MOC 40 mg/kg (ip) up-regulated the progenitor cell proliferation and BDNF level in the same time course. CONLUSION: Up-regulation of the proliferation of hippocampal progenitor cells is one of the action mechanisms for MOC, which may be closely related to the elevation of BDNF level at the same time. These results also extend evidence for our hypothesis that up-regulation of the hippocampal neurogenesis is one of the common mechanisms for antidepressants.

关 键 词：antidepressants MOCLOBEMIDE NEUROGENESIS STRESS brain-derived neurotrophic factor N-METHYLASPARTATE 

分 类 号：R651[医药卫生—外科学] R338[医药卫生—临床医学]