1999 Fiscal Year Final Research Report Summary
Roles of Microglia In Developing brain functions
| Project/Area Number |
09680774
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Fujita Health University |
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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)
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| Project Period (FY) |
1997 – 1999
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| Keywords | microglia / gene transfection / brain-specific / brain development / brain function |
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| 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.
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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[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)
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[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)
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[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)
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