• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2002 Fiscal Year Final Research Report Summary

Cloning of cDNA candidates enforcing brain-specific entry in microglia

Research Project

Project/Area Number 13680854
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 Univ., Inst. For Comprehensive Med. Sci., JRDTAID, Professor, 総合医科学研究所, 教授 (10187297)

Project Period (FY) 2001 – 2002
KeywordsMicroglia / gene transformation / brain-specific / drug delivery system / pharge display / blood-brain barrier
Research Abstract

The ability to manipulate the expression of genes within the mammalian brain provide unique opportunities to study and potentially treat neurologic disorders. To express certain genes specifically in brain has been done with viral vectors or cells carrying DNA, however, they all needed a surgical operation. Recently we found that microglia could enter specifically in brain when injected intra-arterially, and demonstrated that intra-arterial injection of microglia transfected with the lacZ gene resulted in expression of b-galactosidase up to three weeks post-injection in rat brain. This method will allow us to easily deliver the gene of interest to brain without any effects to other organs. In the present study, we compared migration of systemically injected microglia into normal brain vs. ischaemic brain using a model of ischaemic hippocampal lesion. Microglia were labeled by a fluorescent dye using our standard phagocytosis procedure of microscopic particles and then injected intra- arterially into Mongolian gerbils subjected to ischaemia 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 ischaemic lesions were confirmed histochemically to be microglia. Since peripherally injected microglia exhibit specific affinity for ischaemic brain lesions and does not exacerbate ischaemic neuronal injury in the present model, we suggest that microglia may have a potential to be used as a piggy-back ride to deliver therapeutic genes and/or drugs for CNS repair following transitory global ischaemic insult. Now we are trying to isolate gene(s) which product(s) are responsible for brain-specific entry of microglia by pharge-display screening system.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Sawada M ほか: "Brain-Specific Migration and Protective Roles in Brain Damage of Microglia"Advance in Behavioral Biology. 53. 217-220 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohara, Y ほか: "Distinct cell death mechanisms by Theiler's murine encephalomyelitis virus (TMEV) infection in microglia and macrophage"Neurosci Lett.. 327. 41-44 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Salimi, K ほか: "Glial cell line-derived neurotrophic factor enhances survival of GM-CSF dependent rat GMIR1-microglial cells"Neurosci. Res. 43. 221-229 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Frederik Vilhardt ほか: "The HIV-1 Nef protein and phagocyte NADPH oxidase activation"J Biol Chem. 277. 42136-42143 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kenji F.Tanaka ほか: "Existence of functional b_1-and b_2 -adrenergic receptors on microglia"J Neurosci Res. 70. 232-237 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sawada M, Imai F and Suzuki H.: "Brain-Specific Migration and Protective Roles in Brain Damage of Microglia"Advance in Behavioral Biology.. 53. 217-220 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohara, Y., Himeda, T., Asakura, K., Sawada, M.: "Distinct cell death mechanisms by Theiler's murine encephalomyelitis virus (TMEV) infection in microglia and macrophage"Neurosci. Lett.. 327. 41-44 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Salimi, K., Moser, K., Zassler, B., Reindl, M., Embacher, N., Schemer, C., Weis, C., Marksteiner, J., Sawada, M., Humpel, C: "Glial cell line-derived neurotrophic factor enhances survival of GM-CSF dependent rat GMIR1-microglial cells"Neurosci. Res.. 43. 221-229 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Frederik Vilhardt, Olivier Plastre, Makoto Sawada, Kazuo Suzuki, Maciej Wiznerowicz, Etsuko Kiyokawa, Didier Trono, and Karl-Heinz Krause: "The HIV-1 Nef protein and phagocyte NADPH oxidase activation"J. Biol. Chem.. 277. 42139-42143 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kenji F. Tanaka, Haruo Kashima, Hiromi Suzuki, Kenji Ono, Makoto Sawada: "Existence of functional_1-and_2-adrenergic receptors on microglia"J Neurosci. Res.. 70. 232-237 (2002)

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

URL: 

Published: 2004-04-14  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi