Transplantation of neural stem cells overexpressing glial cell line-derived neurotrophic factor enhances Akt and Erk1/2 signaling and neurogenesis in rats after stroke / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 1302-1309, 2013.
Article
in English
| WPRIM (Western Pacific)
| ID: wpr-342185
Responsible library:
WPRO
ABSTRACT
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Grafting GDNF/NSCs enhances neurogenesis and activates Akt and Erk1/2 signaling, that may provide the potential for GDNF/NSCs in stroke treatment.</p>
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Phosphorylation
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Physiology
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Therapeutics
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Rats, Sprague-Dawley
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Mitogen-Activated Protein Kinase 1
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Stroke
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Cell Biology
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Stem Cell Transplantation
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Mitogen-Activated Protein Kinase 3
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Proto-Oncogene Proteins c-akt
Limits:
Animals
Language:
English
Journal:
Chinese Medical Journal
Year:
2013
Document type:
Article