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NEUROTROPHIC ACTIVITY OF CYTOKINE-ACTIVATED ASTROCYTES

Research Project

Project/Area Number 05671183
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionSCHOOL OF MEDICINE,KEIO UNIVERSITY

Principal Investigator

YOSHIDA Kazunari  Sch.of Med.Keio Univ.Instructor, 医学部, 助手 (70166940)

Co-Investigator(Kenkyū-buntansha) SASAKI Hikaru  Sch.of Med.Keio Univ.Assistant, 医学部, 助手 (70245512)
INABA Makoto  Sch.of Med.Keio Univ.Assistant, 医学部, 助手 (00245507)
KAMIGUCHI Hiroyuki  Sch.of Med.Keio Univ.Assistant, 医学部, 助手 (10233933)
WAKAMOTO Hirooki  Sch.of Med.Keio Univ.Assistant, 医学部, 助手 (30230923)
SAGOH Masachika  Sch.of Med.Keio Univ.Assistant, 医学部, 助手 (60215704)
各務 宏  慶應義塾大学, 医学部, 助手 (80255471)
大谷 光弘  慶應義塾大学, 医学部, 助手 (80051605)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Keywordsneurotrophic factor / astrocyte / cytokine / neural regeneration / astrocyte / nerve growth factor / cytokine / neurotrophic factor / cholinergic neuron / interleukin-1 / tumer necresis factor / fibroblaot growth factor / 神経成長因子 / 線維芽細胞成長因子 / インターロイキン-1 / コリン作動性神経細胞 / 副腎皮質ホルモン
Research Abstract

1. Nerve growth kfactor (NGF) and non-NGF-type neurotrophic activities have been found to accumulate transiently in cerebrospinal fluid following surgery. These neurotrophic activites are probably important in the regeneration of damaged neural networks in the central nervous system.
2. A novel neurotrophoc factor which enhances choline acetyltranferase activity of brainstem cholinergic neurons has been shown to exist in astrocyte-conditioned medium. Cytokines such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and acidic fibroblast growth factor (aFGF) increased an amount of the factor released from astrocytes. The factor was revealed to be a heparin-binding protein with a molecular weight of 40-60 kD.
3. Three isoforms (18,22 and 24 kD) of basic fibroblast growth factor (bFGF) are known to be expressed in astrocytes. We have shown that the expression of 22,24-kD isoforms but not of 18-kD isoform in astrocytes is enhanced by cytokines such as IL-1beta, TNF-alph … More a and epidermal growth factor (EGF), and that the bFGF content in the cytoplasm of astrocytes is initially ncreased by these cytokines followed by nuclear targeting and localization. In addition, 22-kD isoform has been shown to be released from astrocytes.
4. We have demonstrated that ciliary neurotrophic factor (CNTF) can be released from astrocytes, and that cytokines such as IL-1beta, TNF-alpha and EGF increase CNTF release kfrom astrocytes.
5. Transkforming growth factor-beta1 (TGF-beta1) has been shown to enhance the expression of neural cell adhesion molecule (NCAM) on astrocytes.
These results indicate that as trocytes secrete various neurkotrophicfactors including a novel non-NGF-type neurotrophic factor (s) and so-called non-secretory factors such as bFGF and CNTF,and that the cytokines, which are lilely to be present in the brain following injury, may play an important role in the repair of damaged neunal networks by increasing the expression or release of these neurotrophic factors and cell adhesion molecules by astrocytes Less

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] 上口裕之: "培養アストロサイトにおけるbasic fibroblast growth factorおよびciliary neurotrophic factorの発現・放出に関する研究-特にcytokineの影響について-" 慶應医学. 72. T457-T470 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masachika Sagoh et al: "Accumulationof nerve growth factor in cerebrospinal fluid and biological activity following neurosurgery" Neurol Med Chir. 37. 431-437 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 稲葉真 他: "サイトカインによるアストロサイトにおける神経細胞接着分子(NCAM)の発現調節" 神経免疫研究. 8. 139-144 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 上口裕之 他: "培養アストロサイトにおけるbFGF isoformの発現パターンおよび細胞内局在におよぼすサイトカインの影響" 神経組織の成長・再生・移植. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hiroyuki Kamiguchi et al: "Release of ciliary neurotrophic factor from cultured astrocytes and its modulation by cytokines" Neurochem Res. 20. 1187-1193 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 左合 正周: "培養アストロサイト由来 神経栄養因子の生理活性" 慶應医学. 72. 365-377 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kamiguchi H,Yoshida K,Sagoh M,Sasaki H,Inaba M,Wakamoto H,Otani M,Toya S.: "Release of ciliary neurotrophic factor from cultured astrocytes and its modulation by cytokines." Neurochem Res. 20. 1187-1193 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kamiguchi H: "Expression and Release of basic fibroblast growth factor and ciliary neurotrophic factor by cytokine-activated astrocytes in culture." Keio Igaku. 72. T457-T470 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sagoh M: "Biological activity of astrocyte-derived neurotrophic factors" Keio Igaku. 72. 365-377 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sagoh M,Yoshida K,Wakamoto H,Kamiguchi H,Otani M,Shiobara R,Toya S: "Accumulation of nerve growth factor in cerebrospinal fluid and biological activity following neurosurgery." Neurol Med Chir. 35. 431-437 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Inaba M,Yoshida K,Asou H,SaAsaki H,Sagoh M,Wakamoto H,Kamiguchi H,Otani M,Toya S: "Regulation of NCAM expression in astrocytes by cytokines." Neuroimmunol Res. 8. 139-144 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kamiguchi H,Yoshida K,Shimazaki K,Inaba M,Sasaki H,Kagami H,Otani M,Toya S: "Effects of cytokines on the expression of bFGF isoforms and their subcellular Iocalization in cultured astrocytes." Jpn Soc Neural GRT. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hiroyuki Kamiguchi et al: "Release of ciliary neurotrophic factor cultured astrocytes and its modulation by cytokines" Neurochem Res. 20. 1187-1193 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 上口裕之: "培養アストロサイトにおけるbasic-fibroblast growth factorおよびciliaty neurotrophic factorの発現・放出に関する研究-特にcytokineの影響について-" 慶鷹医学. 72. T457-T470 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 左合正周: "培養アストロサイト由来神経栄養因子の生理活性" 慶鷹医学. 72. 365-377 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Masachika Sagoh et al: "Accumulation of nerve growth factor in cerebrospinal fluid and biological activity following neurosurgery" Neurol Med Chir. 37. 431-437 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 稲葉真 他: "サイトカインによるアストロサイトにおける神経細胞接着分子(NCAM)の発現調節" 神経免疫研究. 8. 139-144 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 上口裕之 他: "培養アストロサイトにおけるbFGF isoformの発現パターンおよび細胞内局在におよぼすサイトカインの影響" 神経組織の成長・再生・移植. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] 吉田一成、他: "Sodum butyrateを用いたラット胎仔脳神経細胞の選択培養系とそのneurotrophic factorのassay systemsdwの有用性" 神経組織の成長・再生・移植. 6. 7-8 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 左合正周、他: "中隔野および脳幹コリン作動性ニューロンに対するアストロサイトの神経栄養効果" 神経組織の成長・再生・移植. 6. 29-30 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Yoshida,et al.: "Regulation of NGF and NCAM expression in astrocytes by cytokines andglucocorticoid" Neurochemical Research. 19. 892 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 左合正周、他: "Dibutyryl cyclic AMPにより分化誘導されたアストロサイトのNGF産生と神経栄養効果" 神経化学. 39. 454-455 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 上口裕之、他: "培養アストロサイトにおけるbFAFの産生調節とその生物活性について" 神経化学. 33. 662-663 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Yoshida: "Amelioration of septal cholinergic neuronal degeneration after nerre growth factor deprivation by cyto-kine activated aslrocyte" Recent Advances in Neuro traumatology. 279-282 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 吉田一成: "サイトカインにより活性化されるアストロサイトの神経栄養効果に及ぼすglucocorticoidの作用" 神経組織の再生・成長・移植. 5. 13-14 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 吉田一成: "サイトカイン,glucocorticordによるアストロサイトのNGF,NCAM発現調節" 神経化学. 32. 412-413 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 左合正周: "Cytokineにより活性化されるastrocyteのneurotrophic activity" 神経化学. 32. 396-397 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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