title: Transplantation of neural stem cells overexpressing glial cell line-derived neurotrophic factor enhances Akt and Erk1/2 signaling and neurogenesis in rats after stroke.
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.
  
  
  CONCLUSIONS
  Grafting GDNF/NSCs enhances neurogenesis and activates Akt and Erk1/2 signaling, that may provide the potential for GDNF/NSCs in stroke treatment.
authors.affiliation: Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yuan
authors.forename: Sheng-Jun
authors.initials: SJ
authors.lastname: Wen
authors.forename: Chao-Xian
authors.initials: CX
authors.lastname: Yang
authors.forename: Yuan-Guang
authors.initials: YG
authors.lastname: Pang
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Gao
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
authors.forename: Qiong-Lan
authors.initials: QL
authors.lastname: Yuan
mesh_terms: D000818:Animals; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D020521:Stroke / Q000378:metabolism / Q000628:therapy*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3