| Project/Area Number |
18591594
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Ehime University |
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Principal Investigator |
HATA Ryuji Ehime University, Graduate School of Medicine, Associate Professor (90258153)
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| Co-Investigator(Kenkyū-buntansha) |
ONISHI Takanori Ehime University, Graduate School of Medicine, Professor (70233210)
KUMON Yoshiaki Ehime University, Graduate School of Medicine, Associate Professor (80127894)
TANAKA Jyunya Ehime University, Graduate School of Medicine, Professor (70217040)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | SOCS3 / Cerebral ischemia / Neurogenesis / Neural stem cell / Neurogenesis / cerebral ischemia / neurogenesis / neural stem cell |
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| Research Abstract |
To investigate the effects of suppressors of cytokine signaling 3 (SOCS3) on neural stem cell fate, stem cells were infected with an adenoviral vector expressing SOCS3. Three days later, western blot analysis and immunocytochemical analysis revealed that the protein level of MAP2 and the number of MAP2-positive cells were significantly increased in SOCS3-transfected cells, while the protein level of GFAP and the number of GFAP-positive cells were significantly decreased. Furthermore, promoter assay revealed a significant reduction in the transcriptional level of signal transducer and activator of transcription 3 (Stat3) in the transfected cells. In addition, the mRNA levels of Notch family member (notchl) and inhibitory bHLH factors (hes5 and id3) were significantly up-regulated at one day after overexpression of SOCS3. At three days after transfection, the mRNA level of hes5 was significantly decreased, while that of notchl was still up-regulated. Moreover, all of SOCS3-positive cells expressed Nestin protein but did not express both MAP2 and GFAP proteins. These data indicate that overexpression of SOCS3 induced neurogenesis and inhibited astrogliogenesis in neural stem cells. Our data also show that SOCS3 promoted maintenance of neural stem cells. Furthermore, we evaluated the feasibility of the SOCS3-overexpressing neural stem cells for stroke therapy. Rats were subjected to focal cerebral ischemia for 60 min. Following reperfusion, neural stem cells over-expressing SOCS3 (1.0 x 10^5/5ul) were injected into common carotid artery. One day later, we evaluated the infarct size by TTC staining. However, there was no difference in infarct volume between the SOCS3-treated group and vehicle-treated group. We are now trying to evaluate other methods to transplant NSC into the brain, although we failed to demonstrate the feasibility SOCS3-overexpressing neural stem cells for stroke therapy this time.
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