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Dynamic changes of the gene, protein and neural progenitors in the monkey hippocampus after ischemia

Research Project

Project/Area Number 15390432
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

YAMASHIMA Tetsumori  Kanazawa Univ., Graduate School of Medical Science, Dept.of Restorative Neurosurgery, Associate Professor, 大学院・医学系研究科, 助教授 (60135077)

Co-Investigator(Kenkyū-buntansha) OGAWA Satoshi  Kanazawa Univ., Graduate School of Medical Science, Dept.of Neuroanatomy, Professor, 大学院・医学系研究科, 教授 (90283746)
向田 直史  金沢大学, がん研究所, 教授 (30182067)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 2005: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2004: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2003: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywordsneurogenesis / monkey / hippocampus / cerebral ischemia / neural progenitor / subgranular zone / dentate gyrus / adventitia / 一過性脳虚血 / 神経再生 / 神経幹細胞 / BDNF / PSA-NCAM / 歯状回 / CA1 / 神経細胞死 / アポトーシス / ネクローシス / リソソーム / カルパイン / カテプシン
Research Abstract

The followings are main findings of the past three years, using a model of cerebral injury-global ischemia.
1)We found that ischemia can increase the number of NPC in adult monkey hippocampus similarly to the rodent brain, but the monkey response was much lower than the rodent response-10 times in quantity, and more importantly-15 times in ability to produce neurons (neuronal differentiation) (Mol Cell Neurosci 23:292-301,2003).
2)Further, monkey NPC were unable to replace any neurons in the ischemia-vulnerable CA1 sector (Glia 42;209-224,2003), which suggests that they cannot mediate a clinically-significant effect without an external influence.
3)Recently, we have identified potential molecular explanation for this discrepancy between rodent and monkey NPC-while rodent NPC in CA1 sector express the developmental transcription factors Pax6,Emx2 and Ngn2 that can promote neurogenesis, monkey NPC in CA1 did not express these proteins.
4)Importantly, we have identified a vascular niche around the adventitia of blood vessels that can promote neurogenesis in monkey dentate gyrus but not in CA1 sector (Hippocampus 14:861-875,2004).
5)Lastly, we were the first to describe postischemic NPC upregulation in SVZ of the lateral ventricle, also in the olfactory bulb, and a limited neuronal production in the postischemic monkey neocortex and striatum (J Neurosci Res 81:776-788,2005).
6)Thus, the applicant's group has investigated all major regions in the primate telencephalon with respect to postischemic neurogenesis.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (30 results)

All 2006 2005 2004 2003 Other

All Journal Article (24 results) Publications (6 results)

  • [Journal Article] Differential neurogenic potential of progenitor cells in dentate gyrus and CA1 sector of the postischemic adult monkey hippocampus.2006

    • Author(s)
      Tonchev AB, Yamashima T.
    • Journal Title

      Exp Neurol. 198(1)

      Pages: 101-113

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential neurogenic potential of progenitor cells in dentate gyrus and CA1 sector of the postischemic adult monkey hippocampus.2006

    • Author(s)
      Tonchev AB, Yamashima T.
    • Journal Title

      Exp.Neurol. Jan 17(Epub)(電子版)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Minocycline inhibits oxidative stress and decreases in vitro and in vivo ischemic neuronal damage.2005

    • Author(s)
      Morimoto N, Shimazawa M, Yamashima T, Nagai H, Hara H.
    • Journal Title

      Brain Res. 1044(1)

      Pages: 8-15

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Neuroprotective effects of minocycline against in vitro and in vivo retinal ganglion cell damage.2005

    • Author(s)
      Shimazawa M, Yamashima T, Agarwal N, Hara H.
    • Journal Title

      Brain Res. 1053(1-2)

      Pages: 185-194

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Enhanced proliferation of progenitor cells in the subventricularzone and limited neuronal production in the striatum andneocortex of adult macaque monkeys after global cerebral ischemia.2005

    • Author(s)
      Tonchev AB, Yamashima T, Sawamoto K, Okano H.
    • Journal Title

      J Neurosci Res. 81(6)

      Pages: 776-788

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enhanced proliferation of progenitor cells in the subventricular zone and limited neuronal production in the striatum and neocortex of adult macaque monkeys after global cerebral ischemia.2005

    • Author(s)
      Tonchev AB, Yamashima T, Sawamoto K, Okano H.
    • Journal Title

      J Neurosci Res. 81(6)

      Pages: 776-788

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 神経細胞死のメカニズム -脳虚血からアルツハイマー病へ-2005

    • Author(s)
      小谷 進, 山嶋哲盛
    • Journal Title

      Clinical Neuroscience 23・1

      Pages: 29-34

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adult hippocampal neurogenesis in rodents and primates : endogenous, enhanced, and engrafted.2005

    • Author(s)
      Yamashima et al.
    • Journal Title

      Review in the Neurosciences (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of angiogenic factors by Epstein-Barr virus gene products in nasopharyngeal carcinoma.2004

    • Author(s)
      Yoshizaki T, et al.
    • Journal Title

      Recent Research Development in Cancer 6

      Pages: 311-316

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Metastasizing mixed tumour of the parotid gland presenting as multiple lung metastases.2004

    • Author(s)
      Yoshizaki T et al.
    • Journal Title

      J Laryngol Otol. 118

      Pages: 724-726

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ca2+-dependent proteases in ischemic neuronal death : a conserved 'calpain-cathepsin cascade' from nematodes to primates.2004

    • Author(s)
      Yamashima T.
    • Journal Title

      Cell Calcium (Review) 36(3-4)

      Pages: 285-293

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of estrogen receptor-beta in the postischemic monkey hippocampus.2004

    • Author(s)
      Takahashi N, Tonchev AB, Koike K, Murakami K, Yamada K, Yamashima T, Inoue M.
    • Journal Title

      Neurosci Lett. 369(1)

      Pages: 9-13

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vascular adventitia generatesneuronal progenitors in the monkey hippocampus after ischemia.2004

    • Author(s)
      Yamashima T, Tonchev AB, Vachkov IH, Popivanova BK, Seki T, Sawamoto K, Okano H.
    • Journal Title

      Hippocampus 14(7)

      Pages: 861-875

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vascular adventitia generates neuronal progenitors in the monkey hippocampus after ischemia2004

    • Author(s)
      Yamashima et al.
    • Journal Title

      Hippocampus 14・7

      Pages: 861-875

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Ca2+-dependent proteases in ischemic neuronal death-A conserved ‘calpain-cathepsin cascade' from nematodes to primates2004

    • Author(s)
      Yamashima
    • Journal Title

      Cell Calcium 36・3-4

      Pages: 285-293

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of estrogen receptor-beta in the postischemic monkey hippocampus2004

    • Author(s)
      Takahashi et al.
    • Journal Title

      Neurosci Lett 369・1

      Pages: 9-13

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Modulation of cell growth and matrix metalloproteinase-2 activation of oral squamous cell carcinoma as a function of culture condition with type I collagen.2003

    • Author(s)
      Kinsenn H, Sato H, Furukawa M, Yoshizaki T
    • Journal Title

      Acta Otolaryngol. 123

      Pages: 987-993

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cleavage of syndecan-1 by membrane type matrix metalloproteinase-1 stimulates cell migration.2003

    • Author(s)
      Endo K, et al.
    • Journal Title

      J Biol Chem. 278

      Pages: 40764-40770

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of intercellular adhesion molecule (ICAM)-1 in adenoid cystic carcinoma of the head and neck.2003

    • Author(s)
      Shirai A, et al.
    • Journal Title

      Laryngoscope. 113

      Pages: 1955-1960

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential proliferative response in the postischemic hippocampus, temporal cortex, and olfactory bulb of young adult macaque monkeys.2003

    • Author(s)
      Tonchev AB, Yamashima T, Zhao L, Okano H.
    • Journal Title

      Glia 42(3)

      Pages: 209-224

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Accumulation of microglial cells expressing ELR motif-positive CXC chemokines and their receptor CXCR2 in monkey hippocampus after ischemia-reperfusion.2003

    • Author(s)
      Popivanova BK, Koike K, Tonchev AB, Ishida Y, Kondo T, Ogawa S, Mukaida N, Inoue M, Yamashima T.
    • Journal Title

      Brain Res. 970(1-2)

      Pages: 195-204

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Proliferation of neural and neuronal progenitors after global brain ischemia in young adult macaque monkeys.2003

    • Author(s)
      Tonchev AB, Yamashima T, Zhao L, Okano HJ, Okano H.
    • Journal Title

      Mol Cell Neurosci. 23(2)

      Pages: 292-301

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates.2003

    • Author(s)
      Yamashima T, Tonchev AB, Tsukada T, Saido TC, Imajoh-Ohmi S, Momoi T, Kominami E.
    • Journal Title

      Hippocampus 13(7)

      Pages: 791-800

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcription factor protein expression patterns by neural or neuronal progenitor cells of adult monkey subventricular zone.

    • Author(s)
      Tonchev AB, Yamashima T, Sawamoto K, Okano H.
    • Journal Title

      Neuroscience. 2006 Mar 29 [Epub ahead of print]

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Yamashima T., et al.: "Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates"Hippocampus. 13・7. 791-800 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamashima T. et al.: "Vascular adventitia generates neuronal progenitors in the monkey hippocampus after ischemia"Hippocampus. (印刷中). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamashima T.: "Ca2+-dependent proteases in ischemic neuronal death - A conserved 'calpain-cathepsin cascade' from nematodes to primates"Cell Calcium. (印刷中). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tonchev AB, Yamashima T, Zhao L, Okano HJ, Okano H.: "Proliferation of neural and neuronal progenitors after global brain ischemia in young adult macaque monkeys"Mol Cell Neurosci.. 23・2. 292-301 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tonchev AB, Yamashima T, Zhao L, Okano H: "Differential proliferative response in the postischemic hippocampus, temporal cortex, and olfactory bulb of young adult macaque monkeys"Glia. 42・3. 209-224 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Popivanova BK, Koike K, Tonchev AB, Ishida Y, Kondo T, Ogawa S, Mukaida N, Inoue M, Yamashima T.: "Accumulation of microglial cells expressing ELR motif-positive CXC chemokines and their receptor CXCR2 in monkey hippocampus after ischemia-reperfusion"Brain Res.. 970・1-2. 195-204 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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