Transplantation of neural stem cells overexpressing glial cell line-derived neurotrophic factor enhances Akt and Erk1/2 signaling and neurogenesis in rats after stroke |
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Authors: | YUAN Miao WEN Sheng-jun YANG Chao-xian PANG Yuan-guang GAO Xiao-qing LIU Xiao-qing HUANG Liang |
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Institution: | YUAN Miao (Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China);WEN Sheng-jun (Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China);YANG Chao-xian (Department of Neurobiology, Luzhou Medical College, Luzhou, Sichuan 646000, China);PANG Yuan-guang (Department of Neurobiology, Luzhou Medical College, Luzhou, Sichuan 646000, China);GAO Xiao-qing (Department of Neurobiology, Luzhou Medical College, Luzhou, Sichuan 646000, China);LIU Xiao-qing (Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China);HUANG Liang (Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China); |
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Abstract: | 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 signalregulated kinase 1/2 (Erk1/2) 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 Erk1/2 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 Erk1/2 was observed in the GDNF/NSCs and NSCs groups compared with control group,and phosphorylation level of Erk1/2 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 Erk1/2 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 Erk1/2 signaling,that may provide the potential for GDNF/NSCs in stroke treatment. |
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Keywords: | glial cell line-derived neurotrophic factor neural stem cells transplantation neurogenesis 4kt and Erkl/2 signaling |
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