2004 Fiscal Year Final Research Report Summary
The role of microglia on the development of neurological disorders
| Project/Area Number |
15590886
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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 |
Neurology
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| Research Institution | Nagoya University |
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Principal Investigator |
SUZUMURA Akio Nagoya University, Research Institute of Environmental Medicine, Professor, 環境医学研究所, 教授 (50196896)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Tetsuya Nagoya University, Research Institute of Environmental Medicine, Associate Professor, 環境医学研究所, 助教授 (70335008)
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| Project Period (FY) |
2003 – 2004
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| Keywords | microglia / multiple sclerosis / cytokine / neuronal degeneration |
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| Research Abstract |
In this study we focused to investigation of regulatory mechanisms of microglial functions to clarify the pathophysiology of inflammatory neurological disorders and to search new therapeutic strategies. In the central nervous system, microglia function as antigen presenting cells, and inflammatory cells to induce autoimmune diseases such as multiple sclerosis. We have found the microglia produce IL-12 family cytokines which regulate differentiation of T helper cells (Suzumura et al., 2003,Sonobe et al., 2005). One subpopulation of microglia, designated as type 2 microglia do not prouduce IL-12 family cytokines. For the treatment of MS, only interferon-β is available in JAPAN. We have shown that interferon-β enhances inflammatory functions of microglia which may related to the development of adverse effects including malaise, fever etc. Phosphodiesterase inhibitors, such as ibudilast, effectively inhibit pro-inflammatory effects of interferon-b, suggesting possible effects of combination therapy of interferon and phosphodiesterase inhibitors, for the treatment of MS (Kawanokuchi et al., 2004,Feng et al., 2004). Pituitary adenylate cyclase activating polypeptide(PACAP) and radical scavenger, edalabone also suppressed the pro-inflammatory functions of microgiia and ameliorate clinical scores of experimental autoimmune encephalomyelitis (Kato et al., 2004,Banno et al., 2005).
Microglia are considered to play a critical role in induction of axonal damage. We have found that microglia disturbed energy production in neurons via secreting glutamate. Thus, suppression of glutamate production by activated microglia may be of use for the future strategy to treat MS patients.
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Research Products
(22 results)
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[Journal Article] Production of IL-27 and other IL-12 family cytokines by microglia and their subpopulations.2005
Author(s)
Sonobe, Y., Yawata, I., Kawanokuchi, J., Takeuchi, H., Mizuno, T., Suzumura, A.
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Journal Title
Brain Res. 1040
Pages: 202-207
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Autocrine activation of microglia by tumor necrosis factor-α.2005
Author(s)
Kuno, R., Wang, J., Kawanokuchi, J., Takeuchi, H., Mizuno, T., Suzumura, A.
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Journal Title
J.Neuroimmunol 162
Pages: 89-96
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Autocrine activation of microglia by tumor necrosis factor-α.2005
Author(s)
Kuno, R., Wang, J., Kawanokuchi, J., Takeuchi, H., Mizuno, T., Suzumura, A.
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Journal Title
J Neuroimmunol. 162
Pages: 89-96
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The radical scavenger edaravone prevents oxidative neurotoxicity by peroxynitrite and by activated microglia.2005
Author(s)
Banno, M., Mizuno, T., Kato, H., Zang, G., Kawanokuchi, J., Kuno, R., Jin, S., Takeuchi, H., Suzumura, A.
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Journal Title
Neuropharmacol. 48
Pages: 283-290
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Neuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell death induced by activated microglia.2004
Author(s)
Mizuno, T., Kurotani, T., Komatsu, Y., Kawanokuchi, J., Kato, H., Mits
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Journal Title
Neuropharmacol. 46
Pages: 404-411
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Ibudilast, a nonselective phosphodiesterase inhibitor, regulates Th1/Th2 balance and NKT cell subset in multiple sclerosis.2004
Author(s)
Feng, J., Misu, T., Fujihara, K., Sakoda, S., Nakatsuji, Y., Suzumura, A.
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Journal Title
Multiple Scler. 10
Pages: 494-498
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Ibudilast, a nonselective phosphodiesterase inhibitor, regulates Th1/Th2 balance and NKT cell subset in multiple sclerosis.2004
Author(s)
Feng.J., Misu, T., Fujihara, K., Sakoda, S., Nakatsuji, Y., Fukaura, H., Kikuchi, S., Tashiro, K., Suzumura, A., Ishii, N., Sugamura, K., Nakashima, I., Itoyama, Y.
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Journal Title
Multiple Scler. 10
Pages: 494-498
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Neuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell death induced by activated microglia.2004
Author(s)
Mizuno, T., Kurotani, T., Komatsu, Y., Kawanokuchi, J., Kato, H., Mitsuma, N., Suzumura, A.
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Journal Title
Neuropharmacol. 46
Pages: 404-411
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Occurrence of the spinal reflex due to skin pressure in sudomotor and cutaneous vasoconstrictor nerv system of humans.2003
Author(s)
Okagawa, T., Sugenoya, J., Iwase, S., Mano, T., Suzumura, A., Matsumoto, T., Sugiyama, Y.
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Journal Title
Auton.Neurosci. 105
Pages: 62-70
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Occurrence of the spinal reflex due to skin pressure in sudomotor and cutaneous vasoconstrictor nerve system of humans.2003
Author(s)
Okagawa, T., Sugenoya, J., Iwase, S., Mano, T., Suzumura, A., Matsumoto, T., Sugiyama, Y.
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Journal Title
Auton.Neurosci. 105
Pages: 62-70
Description
「研究成果報告書概要(欧文)」より
