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The effects of SOCS3 on neural stem cell fate and feasibility of the SOCS3-overexpressingneural stem cells for stake therapy

Research Project

Project/Area Number 18591594
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionEhime University

Principal Investigator

HATA Ryuji  Ehime University, Graduate School of Medicine, Associate Professor (90258153)

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)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
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)
KeywordsSOCS3 / Cerebral ischemia / Neurogenesis / Neural stem cell / Neurogenesis / cerebral ischemia / neurogenesis / neural stem cell
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.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (43 results)

All 2007 2006

All Journal Article (16 results) (of which Peer Reviewed: 7 results) Presentation (27 results)

  • [Journal Article] Intravenous Infusion of Dihydroginsenoside Rbl Prevents Compressive Spinal Cord Injury and Ischemic Brain Damage through Upregulation of VEGF and Bcl-xL.2007

    • Author(s)
      Sakanaka M, Zhu P, Zhang Bo, Wen TG, Cao F, Ma YJ, Samukawa K, Mitsuda N, Tanaka J, Kuramoto M, Uno H, Hata R.
    • Journal Title

      Journal of Neurotrauma 24

      Pages: 1037-1054

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects2007

    • Author(s)
      Yoshida T, Hakuba N, Morizane I, Fujita K, Cao F, Zhu P, Uchida N, Kameda K, Sakanaka M, Gyo K, Hata R
    • Journal Title

      Neuroscience 145

      Pages: 923-930

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Ginsenoside Rbl protects against damage to the spiral ganglion cells after cochlear ischemia2007

    • Author(s)
      Fujita K, Hakuba N, Hata R, Morizane I, Yoshida T, Shudou M, Sakanaka M, and Gyo K
    • Journal Title

      Neurosci Lett. 415

      Pages: 113-117

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Intravenous Infusion of Dihydroginsenoside Rbl Prevents Compressive Spinal Cord Injury and Ischemic Brain Damage through Upregulation of VEGF and Bcl-xL2007

    • Author(s)
      Sakanaka, M., Zhu, P., Zhang, Bo., Wen, TC., Cao, F., Ma, YJ., Samukawa, K., Mitsuda, N., Tanaka, J., Kuramoto, M., Uno, H., Hata, R
    • Journal Title

      Journal of Neurotrauma 24

      Pages: 1037-1054

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects2007

    • Author(s)
      Yoshida, T., Hakuba, N., Morizane, I., Fujita, K., Cao, F., Zhu, P., Uchida, N., Kameda, K., Sakanaka, M., Gyo, K., Hata, R
    • Journal Title

      Neuroscience 145

      Pages: 923-30

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Ginsenoside Rb1 protects against damage to the spiral ganglion cells after cochlear ischemia2007

    • Author(s)
      Fujita, K., Hakuba, N., Hata, R., Morizane, I., Yoshida, T., Shudou, M., Sakanaka, M., Gyo, K
    • Journal Title

      Neurosci Lett 415

      Pages: 113-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Intravenous Infusion of Dihydroginsenoside Rb 1 Prevents Compressive Spinal Cord Injury and Ischemic Brain Damage through Upregulation of VEGF and Bcl-xL2007

    • Author(s)
      Sakanaka M, Zhu P, Zhang Bo, Wen TC, Cao F, Ma YJ, Samukawa K, Mitsuda N, Tanaka J, Kuramoto M, Uno H, Hata R.
    • Journal Title

      Journal of Neurotrauma 24

      Pages: 1037-1054

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ginsenoside Rb 1 protects against damage to the spiral ganglion cells after cochlear ischemia2007

    • Author(s)
      Fujita K, Hakuba N, Hata R, Morizane I, Yoshida T, Shudou M, Sakanaka M, and Gyo K
    • Journal Title

      Neurosci Lett 415

      Pages: 113-117

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ginsenoside Rb1 protects against damage to the spiral ganglion cells after cochlear ischemia.2007

    • Author(s)
      Fujita K, Hakuba N, Hata R, Morizane I, Yoshida T, Shudou M, Sakanaka M, Gyo K.
    • Journal Title

      Neurosci Lett. 415

      Pages: 113-7

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects2007

    • Author(s)
      Yoshida T, Hakuba N, Morizane I, Fujita K, Cao F, Zhu P, Uchida N, Kameda K, Sakanaka M, Gyo K, Hata R.
    • Journal Title

      Neuroscience 145

      Pages: 923-30

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Prevention of ischemic neuronal death by intravenous infusion of aginseng saponin,ginsenoside Rb(1),that upregulates Bcl-x(L)expression2006

    • Author(s)
      Zhang B, Hata R, Zhu P, Sato K, Wen TC, Yang L, Fujita H, Mitsuda N, Tanaka J, Samukawa K, Maeda N, and Sakanaka M.
    • Journal Title

      J Cereb Blood Flow Metab 26

      Pages: 708-721

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of neural stem cells2006

    • Author(s)
      Cao F, Hata R, Zhu P, Ma YJ, Tanaka J, Hanakawa Y, Hashimoto K, Niinobe M, Yoshikawa K and Sakanaka M.
    • Journal Title

      J Neurochem. 98

      Pages: 459-70

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of neural stem cells2006

    • Author(s)
      Cao, F., Hata, R., Zhu, P., Ma, YJ., Tanaka, J., Hanakawa, Y., Hashimoto, K., Niinobe, M., Yoshikawa, K., Sakanaka, M
    • Journal Title

      J Neurochem 98

      Pages: 459-70

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rb(1), that upregulates Bcl-x(L) expression2006

    • Author(s)
      Zhang, B., Hata, R., Zhu, P., Sato, K., Wen, TC., Yang, L., Fujita, H., Mitsuda, N., Tanaka, J., Samukawa, K., Maeda, N., Sakanaka, M
    • Journal Title

      J Cereb Blood Flow Metab 26

      Pages: 708-721

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rb(1), that upregulates Bcl-x(L) expression.2006

    • Author(s)
      Zhang B, Hata R, Zhu P, Sato K, Wen TC, Yang L, Fujita H, Mitsuda N, Tanaka J, Samukawa K, Maeda N, Sakanaka M.
    • Journal Title

      J Cereb Blood Flow Metab 26

      Pages: 708-721

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of neural stem cells.2006

    • Author(s)
      Cao F, Hata R, Zhu P, Ma YJ, Tanaka J, Hanakawa Y, Hashimoto K, Niinobe M, Yoshikawa K, Sakanaka M.
    • Journal Title

      J Neurochem. 98

      Pages: 459-70

    • Related Report
      2006 Annual Research Report
  • [Presentation] Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects.2007

    • Author(s)
      Yoshida T, Hata R, Hakuba N, Cao F, Zhu P, Sakanaka M, Gyo K.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka, Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Protective effects of dihydrogeninsenoside Rb1 on ischemic brain damage and compressive spinal cord injury through upregulation of VEGF and Bcl-XL.2007

    • Author(s)
      Hata R, Cao F, Zhu P, Samukawa K, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka, Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Overexpression of Stat3 promotes neuronal cell death through activation of microglia.2007

    • Author(s)
      Hata R, Cao F, Zhu P, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka, Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Microglia promotes astrogliogenesis of the neural stem cells through activating Jak/Stat signaling.2007

    • Author(s)
      Zhu P, Hata R, Cao F, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka, Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Upregulation of syntaxinl in the ischemic cortex following permanent focal ischemia in rats.2007

    • Author(s)
      Cao F, Hata R, Zhu P, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka, Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Targeted disruption of organic cation transporter 3 in mice reduces ischemic brain injury through down-regula tion of IL-6 and MCP-1.2007

    • Author(s)
      Zhu P, Hata R, Ogasawara M, Cao F, Maeyama K, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka, Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Delayed neuronal cell death in the brain stem after transient ischemia in gerbils.2007

    • Author(s)
      Cao F, Hata R, Zhu P, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka, Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] α-synuclein promotes neuronal cell death through the activation of microglia.2007

    • Author(s)
      Hata R, Zhu P, Cao F, Sakanaka M, Tanabe H.
    • Organizer
      International Psychogeriatric Association 25th Anniversary Meeting
    • Place of Presentation
      Osaka, Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Risk of conversion from mild memory impairment to Altzhemier' disease in a Japanese community (from the Nakayama Study).2007

    • Author(s)
      Matsumoto N, Hata R, Ishikawa T, Fukuhara R, Hokoishi K, Ikeda M, Tanabe H.
    • Organizer
      International Psychogeriatric Association 25th Anniversary Meeting
    • Place of Presentation
      Osaka, Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects2007

    • Author(s)
      Yoshida, T., Hata, R., Hakuba, N., Cao, F., Zhu, P., Sakanaka, M., Gyo, K
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Protective effects of dihydrogeninsenoside Rbl on ischemic brain damage and compressive spinal cord injury through upregulation of VEGF and Bcl-XL2007

    • Author(s)
      Hata, R., Cao, F., Zhu, P., Samukawa, K., Sakanaka, M
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Overexpression of Stat3 promotes neuronal cell death through activation of microglia2007

    • Author(s)
      Hata, R., Cao, F., Zhu, P., Sakanaka, M
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Microglia promotes astrogliogenesis of the neural stem cells through activating Jak/Stat signaling2007

    • Author(s)
      Zhu, P., Hata, R., Cao, F., Sakanaka, M
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Upregulation of syntaxinl in the ischemic cortex following permanent focal ischemia in rats2007

    • Author(s)
      Cao, F., Hata, R., Zhu, P., Sakanaka, M
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Targeted disruption of organic cation transporter 3 in mice reduces ischemic brain injury through down-regulation of IL 6 and MCP-12007

    • Author(s)
      Zhu, P., Hata, R., Ogasawara, M., Cao, F., Maeyama, K., Sakanaka, M
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Delayed neuronal cell death in the brain stem after transient ischemia in gerbils2007

    • Author(s)
      Cao, F., Hata, R., Zhu, P., Sakanaka, M
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] α-synuclein promotes neuronal cell death through the activation of microglia2007

    • Author(s)
      Hata, R., Zhu, P., Cao, F., Sakanaka, M., Tanabe, H
    • Organizer
      International Psychogeriatric Association 25th Anniversary Meeting
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Risk of conversion from mild memory impairment to Altzhemier' disease in a Japanese community (from the Nakayama Study)2007

    • Author(s)
      Matsumoto, N., Hata, R., Ishikawa, T., Fukuhara, R., Hokoishi, K., Ikeda, M., Tanabe, H
    • Organizer
      International Psychogeriatric Association 25th Anniversary Meeting
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects2007

    • Author(s)
      Yoshida T, Hata R, Hakuba N, Cao F, Zhu P, Sakanaka M, Gyo K.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism&Function
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Protective effects of dihydrogeninsenoside Rb 1 on ischemic brain damage and compressive spinal cord injury through upregulation of VEGF and Bcl-XL2007

    • Author(s)
      Hata R, Cao F, Zhu P, Samukawa K, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism&Function
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Overexpression of Stat 3 promotes neuronal cell death through activation of microglia2007

    • Author(s)
      Hata R, Cao F, Zhu P, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism&Function
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Microglia promotes astrogliogenesis of the neural stem cells through activating Jak/Stat signaling2007

    • Author(s)
      Zhu P, Hata R, Cao F, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism&Function
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Upregulation of syntaxin 1 in the ischemic cortex following permanent focal ischemia in rats2007

    • Author(s)
      Cao F, Hata R, Zhu P, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism&Function
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Targeted disruption of organic cation transporter 3 in mice reduces ischemic brain injury through down-regulation of IL-6 and MCP-12007

    • Author(s)
      Zhu P, Hata R, Ogasawara M, Cao F, Maeyama K, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism&Function
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Delayed neuronal cell death in the brain stem after transient ischemia in gerbils2007

    • Author(s)
      Cao F, Hata R, Zhu P, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism&Function
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] α-synuclein promotes neuronal cell death through the activation of microglia2007

    • Author(s)
      Hata R, Zhu P, Cao F, Sakanaka M, Tanabe H.
    • Organizer
      International Psychogeriatric Association 25th Anniversary Meeting
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Risk of conversion from mild memory impairment to Altzhemier'd isease in a Japanese community(from the Nakayama Study).2007

    • Author(s)
      Matsumoto N, Hata R, Ishikawa T, Fukuhara R, Hokoishi K, Ikeda M, Tanabe H.
    • Organizer
      International Psychogeriatric Association 25th Anniversary Meeting
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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