Transplantation of neural stem cells overexpressing glial cell line-derived neurotrophic factor enhances Akt and Erkl/2 signaling and neurogenesis in rats after stroke  

作　　者：YUAN Miao WEN Sheng-jun YANG Chao-xian PANG Yuan-guang GAO Xiao-qing LIU Xiao-qing HUANG Liang YUAN Qiong-lan 

机构地区：[1]Department of Anatomy and Neurobiology, Tong3i University School of Medicine, Shanghai 200092, China [2]State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200433, China [3]Department of Neurobiology, Luzhou Medical College, Luzhou, Sichuan 646000, China

出　　处：《Chinese Medical Journal》2013年第7期1302-1309,共8页中华医学杂志（英文版）

基　　金：This study was supported by grants from State Key Laboratory of Medical Neurobiology, Fudan University, and the programs from the Ministry of Science and Technology of China （No. 2010CB945600 and No. 2011CB965100）, the National Natural Science Foundation of China （No. 81070987, No. 30971531）, Shanghai Science Foundation （No. 11PJ1407800）, and National Education Ministry （IRT1168）, International Science ＆ Technology Collaboration Program （No. 2011DF30010）.

摘　　要：Background Our previous studies have indicated that the beneficial effects of grafting neural stem cells （NSCs） overexpressing glial cell line-derived neurotrophic factor （GDNF） in rats after stroke. However, the underlying mechanisms are highly debatable. In this study, we investigated whether neurogenesis, Akt, and extracellular signal- regulated kinase 1/2 （Erkl/2） signaling were involved in this process. Methods Transient ischemic stroke were induced by occluding middle cerebral artery for 2 hours and reperfusion. At 3 days after reperfusion, GDNF/NSCs, NSCs, and vehicle were administered. Immunohistochemical staining was used to evaluate neurogenesis by nestin antibody; phosphorylation of Akt and Erkl/2 was investigated by Western blotting analysis. Results Transplantation of GDNF/NSCs and NSCs significantly increased nestin-positive cells compared to control group （vehicle） from 1 to 7 weeks after reperfusion, and GDNF/NSCs showed stronger effect than NSCs at 2 and 3 weeks after reperfusion. Meanwhile, enhanced phosphorylation level of Erkl/2 was observed in the GDNF/NSCs and NSCs groups compared with control group, and phosphorylation level of Erkl/2 in GDNF/NSCs group was remarkably higher than that of NSCs group at any given time. In contrast, expression of mitogen-activated protein kinase phosphatase-1 （MKP-1）, known as inhibitor of Erkl/2 signaling, was significantly decreased in the GDNF/NSCs and NSCs groups compared with the control group. Moreover, much enhanced and prolonged phosphorylation level of Akt of GDNF/NSCs group was detected compared with control and NSCs group. Conclusion Grafting GDNF/NSCs enhances neurogenesis and activates Akt and Erkl/2 signaling, that may provide the potential for GDNF/NSCs in stroke treatment.Background Our previous studies have indicated that the beneficial effects of grafting neural stem cells （NSCs） overexpressing glial cell line-derived neurotrophic factor （GDNF） in rats after stroke. However, the underlying mechanisms are highly debatable. In this study, we investigated whether neurogenesis, Akt, and extracellular signal- regulated kinase 1/2 （Erkl/2） signaling were involved in this process. Methods Transient ischemic stroke were induced by occluding middle cerebral artery for 2 hours and reperfusion. At 3 days after reperfusion, GDNF/NSCs, NSCs, and vehicle were administered. Immunohistochemical staining was used to evaluate neurogenesis by nestin antibody; phosphorylation of Akt and Erkl/2 was investigated by Western blotting analysis. Results Transplantation of GDNF/NSCs and NSCs significantly increased nestin-positive cells compared to control group （vehicle） from 1 to 7 weeks after reperfusion, and GDNF/NSCs showed stronger effect than NSCs at 2 and 3 weeks after reperfusion. Meanwhile, enhanced phosphorylation level of Erkl/2 was observed in the GDNF/NSCs and NSCs groups compared with control group, and phosphorylation level of Erkl/2 in GDNF/NSCs group was remarkably higher than that of NSCs group at any given time. In contrast, expression of mitogen-activated protein kinase phosphatase-1 （MKP-1）, known as inhibitor of Erkl/2 signaling, was significantly decreased in the GDNF/NSCs and NSCs groups compared with the control group. Moreover, much enhanced and prolonged phosphorylation level of Akt of GDNF/NSCs group was detected compared with control and NSCs group. Conclusion Grafting GDNF/NSCs enhances neurogenesis and activates Akt and Erkl/2 signaling, that may provide the potential for GDNF/NSCs in stroke treatment.

关 键 词：glial cell line-derived neurotrophic factor neural stem cells TRANSPLANTATION NEUROGENESIS 4kt and Erkl/2 signaling 

分 类 号：Q421[生物学—神经生物学] Q463[生物学—生理学]