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Transplantation of neural stem cells overexpressing glial cell line‐derived neurotrophic factor enhances Akt and Erk1/2 signaling and neurogenesis in rats after stroke

Miao-lan Yuan,S. Wen,Chaoxian Yang,Yuanxin Pang,Xiaoqing Gao,Xiaoqing Liu,Liang Huang,Q. Yuan

Published 2013 in Chinese Medical Journal

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 signal‐regulated 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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