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Molecular analyses of neuron-astrocyte-microglia network

Research Project

Project/Area Number 13680845
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionKyushu University

Principal Investigator

NODA Mami  Kyushu University, Grad. Sch. Of Pharm, Assoc. Prof., 薬学研究院, 助教授 (80127985)

Co-Investigator(Kenkyū-buntansha) WADA Keiji  National Center of Neurology and Phychiatry, National Institute of Neuroscience, Director, 神経研究所・疾病研究第4部, 部長(研究職) (70250222)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsmicroglia / neuroprotective drug / glutamate receptor / bradkinin receptor / brain injury / 5-HT_<5A> receptors / signal transduction / psychological disorder / ニューロン / アストロサイト / 受容体 / 神経傷害 / パッチクランプ / PEPA / 腫瘍壊死因子 / 炎症性メディエーター / ブラジキニン / 一酸化窒素
Research Abstract

We tried to investigat the interaction between neuron and glia by mainly analyzing the function of microglia which is far behind among the rest of glial cells.
1) The effects of PEPA (neuroprotective drug) on microglia. Microglial cells play an important role in neurodegenerative diseases and the dementia in AIDS. On the other hand, PEPA was reported to potentiate glutamate-induced currents by modulating flop-type of AMPA-receptors in neurons and had ameliorating effects in ischaemic dysfunction in rat brain. Since microglial cells have AMPA-receptor (Noda et al., 2000), we investigated the effects of PEPA on microglial cells. As a result, PEPA potentiated the AMPA-receptor-induced response in microglia isolated from rat brain. The consequence of these effects were, on the contrary, that PEPA inhibited glutamate-induced TNF-alpha release from microglia. These results suggest that the release of TNF-alpha is neurotoxic, therefore the inhibition of TNF-alpha from microglia may contribute … More to protect neurons.
2) Network between neuron-astrocyte-microglia via bradykinin receptors. Bradykinin is an endogenous peptide which causes pain and inflammation. We found that microglia express bradykinin receptors and their expression pattern changed before and after activation of microglia by treating the cells with bradkinin for 23 hours. We are now investigating which kind of cytokines are released from microglia and has found that at least nitric oxide was released. This result indicate that there are not only interaction between microglia and neuron and astrocyte but also between microglia and microvessels in the brain. These findings will contribute to create new therapeutic drug for brain injury.
Though it was believed as a new glial receptor and turned out to be neuronal receptor, we investigated the signal cascade of a new serotonin receptor subtype (5-HT_<5A>) whose mutation may be related to psychological disorder.
3) Multiple signal transductions of 5-HT_<5A> receptors. We found that 5-HT_<5A> receptors are coupled to multiple signal transductions unlike other 5-HT receptor subtypes. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Higashida H.et al.: "Signal transduction from brakykinin, angiotensin, adrenergic and muscarinic receptors to effector enzymes, including ADP-ribosyl cyclase"Biological Chemistry. 382. 23-30 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashida H.et al.: "Cyclic ADP-ribose as a second messenger revisited from a new aspect of signal transduction from receptors to ADP-ribosyl cyclase"Pharmacology & Therapeutics. 90. 283-296 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashida, H., Hossain, K.Z., Takahagi, H., Noda M.: "Measurement of adenylyl cyclase by separating cyclic AMP on silica gel thin-layer chromatography"Analytical Biochemistry. 308. 106-111 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashida H, Zhang JS, Mochida S, Chen XL, Shin Y, Noda M.et al.: "Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells"J.Neurochemistry. 85. 1148-1158 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noda M, Kariura Y, Amano T, et al.: "Expression and function of bradykinin receptors in microglia"Life Sciences. 72. 1573-1581 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noda M, Yasuda S, Okada M, et al.: "Recombinant human 5-HT_<5A> receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways"J.Neurochemistry. 84. 222-232 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nisikawa, K., Li, hang, Kawamura, R., Osaka, H., Wang, Y-L., Hara, Y, Hirokawa, T., Manago, Y., Amano, T., Noda, M., Aoki, S., Wada, K.: "Alterations of structure and hydrolase activity of parkinsonism-associated human ubiquitin carboxyl-terminal hydrolase L1 variants"Biochem Biohys Res Commun. 304. 176-183 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 野田百美, 前野浩巳, 和田圭司: "感覚器官と脳内情報伝達処理、(分担執筆:グルタミン酸トランスポーター)"共立出版. 260(8) (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashida,H., Yokoyama,S., Hoshi,N., Hashii,M., Egorova,A., Zhong,Z-G., Noda,M., Shahidullah,M., Taketo,M., Yasuhiro,K., Takahashi,H., Chen,X-L., Shin,Y., and Zhang,J-S.: "Signal transduction from brakykinin, angiotesin, adrenergic and muscarinic receptors to effector enzymes, including ADP-ribosy1 cyclase"Biological Chemistry. 382. 23-30 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashida,H., Hashii,M., Yokoyama,S., Hoshi,N., K-L. Chen, X-L., Egorova,A., Noda,M., and Zhang,J-S.: "Cyclic ADP-ribose as a second messenger revisited from a new aspect of signal transduction from receptors to ADP-ribosyl cyclase"Pharmacology & Therapeutics. 90. 283-296 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashida,H., Hossain,K.Z., Takahagi,H., and Noda,M.: "Measurement of adenylyl cyclase by separating cyclic AMP on silica gel thin-layer chromatography"Analytical Biochemistry. 308. 106-111 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noda,M., Kariura,Y., Amano,T., Manago,Y., Nishikawa,K., Aoki,S., and Wada,K.: "Life Sciences"72. 72. 1573-1581 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noda,M., Yasuda,S., Okada,M., Higashida,H., Shimada,A., Iwata,N., Ozaki,N., Nishikawa,K.., Shirasawa,S., Uchida,M., Aoki,S., Wada,K.: "Recombinant human 5-HT_<5A> receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways"J. Neurochemistry. 84. 222-232 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishikawa,K., Li,hang., Kawamura,R., Osaka,H., wang, Y-L., Hara,Y., Hirokawa,T., Manago,Y., Amano,T., Noda,M., Aoki,S., Wada,K.: "Alterations of structure and hydrolase activity of parkinsonism-hydrolase L1 variants"Biochem Biohys Res Commun. 304. 176-183 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashida,H., Zhang,JS., Mochida,S., Chen XL., Shin,Y., Noda,M., Hossain,KZ., Hoshi,N., Hashii,M., Shigemto,R., Nakanishi,S., Fukuda,Y., Yokoyama,S.: "Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells"J. Neurochemistry. 85. 1148-1158 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noda,M., Maeno,H., Wada,K.: "Glutamate transporter"Sensory Organ and Signal Transduction System in the Brain, Kyouritsu Shuppan, (in total 260 pages). 100-107 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noda M, Yasuda S, Okada M, et al.: "Recombinant human 5-HT_<5A> receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways"J.Neurochemistry. 84. 222-232 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Noda M, Kariura Y, Amano T, et al.: "Expression and function of bradykinin receptors in microglia"Life Sciences. 72. 1573-1581 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Higashida H, Hossain KZ, Takahagi H, Noda M.: "Measurement of adenylyl cyclase by separating cyclic AMP on silica gel thin-layer chromatography"Biochemistry. 308. 106-111 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Higashida H, Zhang JS, Yokoyama S, Noda M. et al.: "Sympathetic potentiaion of cyclic ADP-ribose formation in rat cardiac myocytes"Advances In Behavioral Biology. 53. 73-76 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Higashida H, Zhang JS, Mochida S, Chen XL, Shin Y, Noda M. et al.: "Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells"J.Neurochemistry. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] 野田百美, 前野浩巳, 和田圭司: "感覚器官と脳内情報伝達処理、(分担執筆:グルタミン酸トランスポーター)"共立出版. 260(8) (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Higashida H. et al.: "Signal transduction from brakykinin, angiotensin, adrenergic and muscarinic receptors to effector enzymes, including ADP-ribosy1 cyclase"Biological Chemistry. 382. 20-33 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Noda M.: "Neuron-microglia interaction via glutamate"Neurochemical Research. 26. 275 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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