抗抑郁剂对慢性应激小鼠海马神经元再生的影响

Effect of antidepressants on the hippocampal neurogenesis in chronically stressed mice

目的 探讨抗抑郁剂作用机制。方法 以流式细胞仪法测定细胞DNA合成期 (S期 )百分率 ;用脑冷冻切片的免疫组化实验检测海马齿状回神经元先祖细胞分裂及脑源性神经营养因子 (BDNF)水平。结果 以N 甲基 D 天冬氨酸(NMDA) 6 0 0 μmol·L-1 处理PC1 2细胞 3d后 ,细胞S期百分率明显降低 ,提示高浓度NMDA可抑制细胞分裂。如果同时给予经典抗抑郁剂去甲丙米嗪 (DIM)或氟西丁 (FLU) 1 ,5 μmol·L-1 则明显提高细胞S期百分率。慢性应激 2 4d小鼠海马齿状回颗粒细胞层下区的先祖细胞分裂减2 0 0 3 10 10收稿 ,2 0 0 3 12 17修回 国家自然科学基金资助课题 ,No 3 0 3 0 0 419;北京市自然科学基金资助课题 ,No 70 42 0 5 2作者简介 :李云峰 ,男 ,3 1岁 ,博士 ,副研究员。研究方向 :精神药理学。Tel:0 10 6687460 6 5 ,Fax:0 10 682 1165 6,E mail:lyf619@yahoo .com .cn ;罗质璞 ,男 ,66岁 ,研究员。研究方向 :精神药理学。Tel:0 10 6693 1619 1,Fax :0 10 682 1165 6少 ,同时BDNF水平低下 ,均表现为阳性棕色颗粒缺失 ,若同时给予DIM或FLU 1 0mg·kg-1 (ip)则逆转上述现象 ,明显增加先祖细胞的分裂和BDNF水平 ,二者在时程上一致。结论 促进海马齿状回神经元再生可能是抗抑郁剂共同作用机制之一 。

AIM To explore possible action mechanism of antidepressants. METHODS Using flow cytometry, the cell proliferation was detected. The proliferation of hippocampal progenitor cells and level of brain derived neurotrophic factor (BDNF) were measured by immunohistochemistry. RESULTS Treatment with N methyl D aspartate (NMDA) 600 μmol·L -1 for 3 d significantly decreased the percentage of S phase in PC12 cells, while in the presence of classical antidepressants, desipramine (DIM) or fluoxetine (FLU) 1, 5 μmol·L -1 , the percentage of S phase increased. Furthermore, the proliferation of hippocampal progenitor cells, as well as the BDNF level in dentate gyrus (subgranular zone) significantly decreased in chronically stressed mice for 24 d, while chronic administration with DIM or FLU 10 mg·kg -1 (ip) normalized it. Meanwhile, the BDNF level in dentate gyrus also elevated after DIM or FLU treatments. CONCLUSION Up regulation of the hippocampal neurogenesis is the common action mechanism for antidepressants, which may be closely related to the elevation of BDNF level at the same time.