Transplantation of neural stem cells overexpressing glial cell line-derived neurotrophic factor enhances Akt and Erk1/2 signaling and neurogenesis in rats after stroke
10.3760/cma.j.issn.0366-6999.20122965
- Author:
Miao YUAN
1
;
Sheng-Jun WEN
;
Chao-Xian YANG
;
Yuan-Guang PANG
;
Xiao-Qing GAO
;
Xiao-Qing LIU
;
Liang HUANG
Author Information
1. Department of Anatomy and Neurobiology
- Keywords:
glial cell line-derived neurotrophic factor;
neural stem cells;
transplantation;
neurogenesis;
Akt and Erk1/2 signaling
- From:
Chinese Medical Journal
2013;(7):1302-1309
- CountryChina
- Language:Chinese
-
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.
