2003 Fiscal Year Final Research Report Summary
Analysis of brain mechanism of fever using molecular probes for PGE synthesizing enzymes and PGE receptors.
| Project/Area Number |
13470011
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | Kyoto University |
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Principal Investigator |
MATSUMURA Kiyoshi Kyoto Univ., Grad. Sch. Informatics, Associate professor, 情報学研究科, 助教授 (10157349)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMURA Kyoko Hyogo Univ., Teacher Education, Dept. of Life and Health, Sciences, Professor, 学校教育学部, 教授 (40173877)
HOSOKAWA Hiroshi Kyoto Univ., Grad. Sch. Informatics, Research Associate, 情報学研究科, 助手 (90359779)
KOBAYASHI Shigeo Kyoto Univ., Grad. Sch. Informatics, Professor, 情報学研究科, 教授 (40124797)
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| Project Period (FY) |
2001 – 2003
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| Keywords | prostaglandin E synthase / cyclooxygenase / fever / brain endothelial cells / medullary raphe nucleus / brown adipose tissue / prostaglandin receptor / GABA |
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| Research Abstract |
1, Expression of microsomal prostaglandin E' synthase (mPGES) in the brain and its physiological significance.
・We cloned rat mPGES cDNA.
・mPGES mRNA and its protein were induced in brain endothelial cells in response to lipopolysaccharide (LPS)
・Induced mPGES and cyclooxygenase 2 (COX 2) were colocalized in the perinuclear region of brain endothelial cells.
・A COX-2-specific inhibitor suppressed elevation of PGE2 level in the cerebrospinal, fluid (CSF).
・Time courses of COX 2 and mPGES expression in brain endothelial cells were well correlated with that of fever and PGE2 level in the CSF.
・mPGES gene deficient mice did not develop fever in response to LPS, and other pyrogenic stimuli.
・Isolated subarachnoidal brain blood vessels with meninges from LPS pretreated rats produced more PGE2 than those from saline-pretreated rats. The relative increase in PGE2 production by LPS pretreatment was most prominent among other prostanoids tested.
・These results indicate that 'mPGES induced in brain endot
… More
helial'cells is involved in fever.
2, Efferent neural pathway from PGE2 receptor to a thermogenic organ, brown adipose tissue (BAT).
・Injection of PGE2 into the cerebral ventricle or preoptic area induced elevation of BAT temperature and FOS expression in the medullary raphe nucleus (raphe pallidus; RPa).
・Elevation of BAT temperature by PGE2 was completely suppressed by an injection of muscimol, a GABA agonist, into the RPa.
・Retrograde and anterograde neural tracing revealed a direct projection of EP3 (a PGE2 receptor subtype)-bearing cells in the preoptic area to the RPa.
・A part of EP3bearing cells in the preoptic area were GABAergic.
・In the Rpa, neurons expressing vesicular glutamate transporter 3 (VGLUT3) projected to the sympathetic preganglionic neurons in the intermediolateral nucleus of the spinal cord.
・Collectively, these results revealed a neural. efferent pathway for fever originating from the EP3 bearing cells in the preoptic area to the BAT through RPa and sympathetic nervous system. Less
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Research Products
(24 results)
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[Publications] Nakamura, K., Matsumura, K., Kaneko, T., Kobayashi, S., Hironori, K., Negishi, M.: "The rostral raphe pallidus nucleus mediates pyrogenic transmission from the preoptic area"J.Neurosci.. 22. 4600-4610 (2002)
Description
「研究成果報告書概要(和文)」より
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[Publications] Okazawa, M., Takao, K., Hori, A., Shiraki, T., Matsumura, K., Kobayashi, S.: "Ionic basis of cold receptors acting as thermostats"J.Neurosci.. 22. 3994-4001 (2002)
Description
「研究成果報告書概要(和文)」より
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[Publications] Inoue, W., Matsumura, K., Yamagata, K, Takemiya, T., Shiraki, T., Kobayashi, S.: "Brain-specific endothelial induction of prostaglandin E2 synthesis enzymes and its temporal relation to fever"Neurosci.Res.. 44. 51-61 (2002)
Description
「研究成果報告書概要(和文)」より
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[Publications] Ozaki-Okayama, Y., Matsumura, K., Ibuki, T., Ueda, M., Yamazaki, Y., Tanaka, Y., Kobayashi, S.: "Burn injury enhances brain prostaglandin E2 production through induction of cyclooxygenase-2 and microsomal prostaglandin E synthase in cerebral vascular endothelial cells in rats"Crit.Care Med.. 32. 795-800 (2004)
Description
「研究成果報告書概要(和文)」より
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[Publications] Nakamura, K., Matsumura, K., Hubschle, T., Nakamura, Y., Hioki, H., Fujiyama, F., Boldogkoi, Z., Konig, M., Thiel, H.-J., Gerstberger, R., Kobayashi, S., Kaneko T.: "Identification of Sympathetic Premotor Neurons in Medullary Raphe Regions Mediating Fever and Other Thermoregulatory Functions"J.Neurosci.. In press. (2004)
Description
「研究成果報告書概要(和文)」より
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[Publications] Nakamura, K., Matsumura, K., Kaneko, T., Kobayashi, S., Hironori, K., Negishi, M.: "The rostral raphe pallidus nucleus mediates pyrogenic transmission from the preoptic area"J. Neurosci.. 22. 4600-4610 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Okazawa, M., Takao, K., Hori, A., Shiraki, T., Matsumura, K., Kobayashi, S.: "Ionic basis of cold receptors acting as thermostats"J. Neurosci.. 22. 3994-4001 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Inoue, W., Matsumura, K., Yamagata, K., Takemiya, T., Shiraki, T., Kobayashi, S.: "Brain-specific endothelial induction of prostaglandin E2 synthesis. enzymes and its temporal relation to fever"Neurosci, Res.. 44. 51-61 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ozaki-Okayama, Y., Matsumura, K., Ibuki, T., Ueda, M., Yamazaki, Y., Tanaka, Y., Kobayashi, S.: "Burn injury enhances brain prostaglandin E2 production, through induction of cyclooxygenase 2 and microsomal prostaglandin E synthase in cerebral vascular endothelial cells in rats"Crit. Care Med.. 32. 795-800 (2004)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Nakamura, K.., Matsumura, K., Hubschle, T., Nakamura, Y., Hioki, H., Fujiyama, F., Boldogkoi, Z., Konig, M.: "Thiel, H. J., Gerstberger, R., Kobayashi, S., Kaneko T., Identification of Sympathetic Premotor Neurons in Medullary Raphe Regions Mediating Fever and Other Thermoregulatory Functions"J. Neurosci.. (in press). (2004)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Matsumura, K., Inoue, W.., Okamura, R., Kawaguchi, H., Kobayashi, S.: "Communication between brain and immune system, In Cerebral ventricle and associated organs. (Japanese)"Burehn Shuppan. (2003)
Description
「研究成果報告書概要(欧文)」より
