雌二醇通过BDNF促进端脑神经细胞增殖与分化

Estradiol induce neural proliferation and differetiation through regulating the expression of BDNF

目的探讨雌二醇(E_2)在神经组织中的作用机制,分析E_2对神经细胞增殖及神经元分化的影响,以及其是否由脑源性神经营养因子(BDNF)介导。方法离体条件下培养动物端脑神经组织,设置各实验组,分别以E_2、E_2受体抑制剂、BDNF、BDNF抗体或以上试剂联合处理,之后进行相关免疫组织化学染色分析不同处理条件下神经细胞的增殖、神经元分化情况;在此基础上通过实时荧光定量PCR检测E_2能否调节BDNF基因的表达。结果 E_2和BDNF均能促进新生神经细胞的产生,增加Hu+神经元数目,E_2受体抑制剂及BDNF抗体则有相反作用;并且E_2的作用效果能被BDNF抗体消减,而E_2受体抑制剂不能影响BDNF正常发挥作用;实时荧光定量PCR实验结果显示,E_2能显著上调BDNF mRNA的表达,而E_2受体抑制剂能抑制BDNF mRNA表达。结论体外培养条件下,E_2对神经组织内细胞增殖、神经元分化的促进作用可由BDNF介导。

Objective To address the influences of estradiol on the proliferation and neuronal differentiation in neural tis- sues,and then analyse whether BDNF involves in the pathway of this estradiol-induced cell division and specification. Methods The forebrain tissues of experimental animals were cultured in vitro, and treated respectively with estradiol,estrogen receptor inhibitor, BDNF,BDNF antibody,or received a combined treatment. And the immunohistochemistry was performed to reveal the situation of cell proliferation,neuronal differentiation in different experimental groups. Then real-time PCR was carried out to detect whether the expression of BDNF was regulated by estradiol. Results Both estradiol and BDNF increased the newborn cells and Hu positive neurons in cultured tissues, estrogen receptor inhibitor tamoxifen and BDNF antibody decreased the measurements eonversely; the effects of estradiol were diminished by anti-BDNF,while BDNF＇s effect didn＇t changed by tamoxifen. Moreover, the expression of BDNF mRNA were up-regulated by estradiol and were inhibited by estrogen receptor inhibitor. Corlclusion Estradiol might induce neural proliferation and differentiation in vitro by regulating the level of BDNF.