目的探讨死亡受体5(DR5)对神经细胞增殖的影响。方法采用5一溴脱氧尿嘧啶核苷(BrdU)、DR5、Doublecortin(DCX)等抗体免疫荧光标记法,检测各发育阶段(从胚胎期至生后成年,共100只小鼠)脑组织内DR5阳性细胞的表达变化,以及DR5阳性细胞与神经增殖细胞的关系。结果在胚胎期和新生鼠中,DR5阳性细胞密集分布于海马齿状回颗粒细胞层,呈强表达。7日龄(P7)后,DR5阳性细胞减少,强表达的阳性细胞密集分布在齿状回的下颗粒层,其余颗粒细胞呈弱表达。P30后,在齿状回的下颗粒层仅发现少数DR5阳性细胞,其余颗粒细胞不表达DR5。同时,在其他神经细胞增殖区,如新生鼠(PO)小脑外颗粒区和P7嗅球的喙侧迁移流(RMS)区域,DR5阳性细胞的表达和分布规律均表明,DR5阳性细胞是增殖的神经细胞或有丝分裂后期的新生神经元。进一步的实验发现,齿状回下颗粒层的DR5阳性细胞与BrdU阳性细胞或Doublecortin阳性细胞共存,表明DR5阳性细胞是神经前体细胞和新生神经元。结论DR5阳性细胞是增殖的神经细胞和新生神经元,提示DR5参与神经细胞增殖与分化。
Objective To investigate the influence of death receptor 5 (DR5) in the proliferation of nerve cells. Methods Totally 100 mice from embryonic day (E) 16 to postnatal day (P) 180 were used in the study, brain tissues were visualized for DR5 expression and the relationship between DR5 and neuroproliferation by immunohistochemistry of the bromodeoxyuridine (BrdU) , DR5, doublecortin antibody from embryonic period to adult mice. Results In embryonic and newborn mice, the DR5 positive cells were distributed in granular layer densely with very strong fluorescence. After P7, the number of DR5 positive cells decreased, and the cells with intensive fluorescence were mainly located in subgranular layer, however, the rest of granular cells showed weak fluorescence. After P30, only a few DR5 positive cells were found in subgranular layer, and the granule cells appeared without fluorescence. Similar results were also observed in other proliferative zones, such as P0 cerebellum (external granular zone) and P7 rostral migratory stream of olfactory bulb. All the ceils in those proliferative zones usually were DR5 positive with intensive fluorescence. Its developmental trend and distribution suggested the DR5 positive cells were proliferative ceils or young postmitotic neurons. The further experiments also showed the DR5 positive ceils in subgranular layer were double-stained with BrdU immunolabeling or doublecortin immunolabeling, demonstrating the DR5 positive neurons were neuroprogenitor cells and newborn postmitotic neurons. Conclusion The neuroprogentor cells and newborn neurons are usually DR5 positive cells, suggesting DR5 is involved in neuroproliferation and differentiation.