Association of leptomeningeal and glial cells in the persistent pain
Project/Area Number |
18613010
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pain science
|
Research Institution | Kyushu University |
Principal Investigator |
TAKE Hiro Kyushu University, Faculty of Dental Sciences, Professor (10420598)
|
Co-Investigator(Kenkyū-buntansha) |
NAKANISHI Hiroshi KYUSHU UNIVERSITY, Faculty of Dental Sciences, Professor (20155774)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥4,080,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
Keywords | pain / leptomeninges / inflammatory cytokines / glial cells / patch clamp / NMDA receotors / パッチクランプ / 三叉神経脊髄路核 / 下歯槽神経切断 / アストロサイト |
Research Abstract |
After immunization with the complete Freund's adjuvant (CFA) , cyclooxygenase (COX) -2 and membrane-bound prostaglandin E synthase-1 (mPGES-1) were induced in the leptomeninges. Primary cultured leptomeningeal cells secreted PGE_2 after treatment with lipopolysaccharide (LPS) or proinflammatory cytokines. The LPS-induced release of PGE_2 was depressed by a selective COX-2 inhibitor, NS-398. On the other hand, TGF-β1 and TGF-β receptor II(TGF-βRII)both markedly increased in the leptomeninges and the parenchymal cells after the CFA injection. Double staining immunohistochemistry demonstrated TGF-β1 to be induced in both glial cells and cortical neurons, while TGF-βRII was only induced in cortical neurons. PGE_2 was found to directly increase the production of TGF-β1 and TGF-βRII in the primary cultured cells. These observations strongly suggest that PGE_2, which is biosynthesized by the leptomeninges, mainly regulates the production of TGF-β1 by glial cells and cortical neuron, thus playing a protective role in the cortical neurons during systemic inflammation. Furthermore, we found that IL-1β increased the neuronal excitability by inhibition of ChTX-sensitive K^ca channels activated by Ca^ (2+) influx through both NMDA receptors and voltage-gated Ca^ (2+) channels, contributing to the pathogenesis of persistent pain.
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Report
(3 results)
Research Products
(46 results)
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[Journal Article] Phospholipids modulate superoxide and nitric oxide production by lipopolysaccharide and phorbol 12-myristate-13-acetate-activated microglia.2007
Author(s)
Hashioka, S., Han, Y-H., Fujii, S., Kato, H., Monji, A., Utsumi, H., Sawada, M., Nakanishi, H., Kanba, S
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Journal Title
Neurochem. Int. 50
Pages: 499-506
Description
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[Journal Article] Phosphatidylserine and phosphatidylcholine-containing liposomes inhibit amyloid 13 and interferon-y-induced microglial activation.2007
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Free Rad. Biol. Med. 42
Pages: 945-954
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[Journal Article] Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice.2007
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Yamasaki, R., Zhang, J., Koshiishi, I., Sastradipura Suniarti, D.F., Wu, Z., Peters, C., Schwake, M., Uchiyama, Y., Kira, J.-I., Saftig, P., Utsumi, H., Nakanishi, H
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Mol. Cell. Neurosci. 35
Pages: 573-584
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[Journal Article] Involvement of COX-1 and up-regulated prostaglandin E synthases in phosphatidylserine liposome-induced prostaglandin E2 production of microglia.2006
Author(s)
Zhang, J., Fujii, S., Hashioka, S., Tanaka, Y., Wu, Z., Shiratsuchi, A., Nakanishi, Y., Nakanishi, H
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Journal Title
J. Neuroimmunol. 172
Pages: 112-120
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[Journal Article] The intra-arterial injection of microglia protects hippocampal CA1 neurons against global ischemia-induced functional deficits in rats.2006
Author(s)
Hayashi, Y., Tomimatsu, Y., Suzuki, H., Yamada, J., Yao, H., Kagamiishi, Y., Tateishi, N., Sawada, M., Nakanishi, H
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Journal Title
Neuroscience 142
Pages: 87-96
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