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1999 Fiscal Year Final Research Report Summary

Roles of Microglia In Developing brain functions

Research Project

Project/Area Number 09680774
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SAWADA Makoto  Fujita Health University, Institute for Comprehensive Medical Science, Associate Professor, 総合医科学研究所, 助教授 (10187297)

Project Period (FY) 1997 – 1999
Keywordsmicroglia / gene transfection / brain-specific / brain development / brain function
Research Abstract

Microglia, macrophage-like cells in the brain, are multi-functional cells. I found that microglia had a specific affinity to the brain but macrophages did not. When fluorescent-labeled microglial cells were injected into the aorta of an adult male rat, many fluorescent cells were observed in the brain and few were seen in the liver. These results suggest that microglia have a specific affinity and the ability to migrate to the brain. To determine whether an artificially modified gene could be transferred into brain using our novel technique, microglia were transected with a lacZ gene expression vector and were injected into the aorta of rats. When the brain sections were stained with X-gal, many blue cells were observed thoughout the brains prepared from rats injected with the cells carrying a lacZ gene expression vector. The activity of b-galactosidase was detected in the brain sections from these rats. Next, we compared migration of systemically injected microglia into normal brain vs. ischemic brain using a model of ischemic hippocampal lesion. Microglia were injected intra-arterially into Mongolian gerbils subjected to ischemia reperfusion neuronal injury. Delayed death of pyramidal neurons was confirmed by conventional histological analysis and dUTP nick end labeling (TUNEL) method. Clusters of dye-tagged cells migrating into the hippocampal ischemic lesions were confirmed histochemically to be microglia. Peripherally7 injected microglia exhibit specific affinity for ischemic brain lesions and does not exacerbate ischemic neuronal injury in the present model. Rather we found protective effects of exogenous microglia on delayed death of pyramidal neurons. Therefore, we suggest that microglia may have a potential to be used as a piggy-back ride to deliver therapeutic genes and/of drugs for CNS repair following transitory global ischemic insult.

  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Sawada, M., et al: "IL-10 inhibits both production of cytokines and expression of cytokine receptors in microglia"J Neurochem.. 72. 1466-1471 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ono, K., et al: "Migration of exogenous immature hematopoietic cells into adult mouse brain parenchyma under GFP-expressing bone marrow chimera"Biochem. Biophys. Res. Commun.. 262. 610-614 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzumura, A., et al: "Ibudilast suppresses TNF alpha production by glial cells functioning mainly as type III phosphodiesterase inhibitor in CNS"Brain Res. 837. 203-212 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inoue, H., Sawada M. et al: "Serial analysis of gene expression in a microglial cell line"Glia.. 28. 265-271 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzumura, A., Sawada, M., et al: "Effects of vesnarmone on cytokine production and activation of murine microglia"Life Sciences. 64. 1197-1203 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imai, F., Sawada, M., et al: "Exogenous microglia enter the brain and migrate into ischaemic hippocampal lesions"Newrosci, Lett. 272. 127-130 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makoto Sawada: "Brain-specific gene expression by immortalized microglial cell-mediated gene transfer in the mammalian brain"FEBS Letters. 433. 37-40 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makoto Sawada: "IL-10 inhibits both production of cytokines and expression of cytokine receptors in microglia"J. Neurochem.. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kunihiko Asakura: "Differentiation-specific mRNA expression of a mouse bipotential glial cell line"Neurosci Lett. 258. 21-24 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akihide Takeuchi: "Microglial NO induces delayed neuronal death following acute injury in the striatum"Eur. J. Neuroscience. 10. 1613-1620 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makoto Sawada: "Pathophysiological significance of cytokine network in the brain"Brain and Biodifence (Oomura, Y. and Hori, T. eds). 217-228 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 澤田誠: "神経系の分化とサイトカイン"Clin Neurosci. 16. 406-408 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] F. Imai: "Migration activity of microglia and macrophage into rat brain"Neuroscience Letters. 237. 49-52 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 澤田誠: "ミクログリア細胞株を用いた脳疾患の治療の可能性"日本医事新報. 3844. 28-30 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Tanaka: "Expression of Ly-6C on microglia in the developing and adult mouse brain"Neuroscience Letters. 239. 17-20 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A. Suzumura: "Production of interleukin-12 and expression of its receptors by murine microglia"Brain Research. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 澤田誠: "脳のサイトカインネットワーク"蛋白質・核酸・酵素. 42・3. 504-511 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makoto Sawada: "Changes in gene expression in mouse astrocytes during long-term, serial culture"Tissue Culture Research Communication. 16. 129-135 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sawada,M., Suzumura,A., Hosoya,H., Marunouchi,T., Nagatsu,T.: "IL-10 inhibits both production of cytokines and expression of cytokine receptors in microglia"J.Neurochem. 72. 1466-1471 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ono,K, Takii,T, Onozaki,K, Ikawa,M, Okabe,M, Sawada,M: "Migration of Exogenous Immature Hematopoietic Cells into Adult Mouse Brain Parenchyma under GFP-Expressing Bone Marrow Chimera"Biochem Biophys Res Commun. 262. 610-614 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzumura,A.,Ito,A., Yoshikawa,M., Sawada,M.: "Ibudilast suppresses TNF alpha production by glial cells functioning mainly as type "III" phosphodiesterase inhibitor in the CNS."Brain Res.. 837. 203-212 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inoue,H., Sawada,M., Ryo,A., Tanahashi,H., Wakatsuki,T., Hada,A., Kondoh,N., Nakagaki,K., Takahashi,K., Suzumura,A., Yamamoto,M., Tabira,T.: "Serial analysis of gene expression in a microglial cell line."Glia. 28. 265-271 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Imai,F., Sawada,M., Suzuki,H., et al.: "Exogenous microglia enter the brain and migrate into ischaemic hippocampal lesions."Neurosci. Lett.. 272. 127-130 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzumura,A., Sawada,M., Takayanagi,T.: "Production of interleukin-12 and expression of its receptors by murine microglia"Life Sciences. 64. 1197-1203 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sawada,M., Imai,F., Suzuki,H., Hayakawa,M., Knno,T., Nagatsu,T.: "Brain-specific gene expression by immortalized microglial cell-mediated gene transfer in the mammalian brain"FEBS Lett.. 433. 37-40 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzumura,A., Sawada,M., Takayanagi,T.: "Production of interleukin-12 and expression of its receptors by murine microglia"Brain Research. 787. 139-142 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Asakura,K., Suzumura,A., Rodrigues,M., Sawada,M.: "Differentiation-specific mRNA expression of a mouse bipotential glial cell line."Neurosci. Lett. 258. 21-24 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka,M., Sawada,M., Miura,M., Marunouchi,T.: "Insulin-like growth factor-I analogue prevents apoptosis mediated through an interleukin I-converting enzyme(caspase-1)-like protease of cerebellar external tranular layer neurons : developmental stage-specific mechanisms of neuronal cell death."Neuroscience. 84. 89-100 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeuchi,A., Isobe,K., Miyaishi,O., Sawada,M., Fan,Z.H., Nakashima,I., Kiuchi,K.: "Microglial NO induces delayed neuronal death following acute injury in the striatum."Eur J Neurosci. 10. 1613-1620 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Dong-Ruyl,L., Sawada,M., Nakano,K.: "Tryptophan and its metabolite, kynurenine, stimulate expression of nerve growth factor in cultured mouse astroglial cells."Neurosci.Lett.. 244. 17-20 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzumura,A., Sawada,M., Makino,M.: "Propentofyline inhibits production of TNF_and infection of LP-BMS murine leukemia virus in glial cells."J.Neurovirol. 4. 552-559 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Imai,F., Sawada,M., Suzuki,H., Kiya,N., Hayakawa,M., Nagatsu,T., Marunouchi,T,m Kanno,T.: "Migration activity of microglia and macrophages into rat brain."Neurosci. Lett.. 237. 49-52 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka,M., Marunouchi,T., Sawada,M.: "Expression of Ly-6C on microglia in the developing and adult mouse brain."Neurosci. Lett.. 239. 17-20 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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