| Project/Area Number |
08044300
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
HORI Tetsuro KYUSHU UNIV., DEPT.OF PHYSIOL., PROFESSOR, 医学部, 教授 (00022814)
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| Co-Investigator(Kenkyū-buntansha) |
ARIMURA Akira TULANE UNIV., US-JAPAN BIOMEDICAL RES.LABS., PROFESSOR, 日生物医学研究所, 教授
SIMON Eckhar マックスプランク生理学臨床研究所, 教授
TAKAKI Atsushi KYUSHU UNIV., DEPT.OF PHYSIOL.ASSISTANT, 医学部, 助手 (30243934)
KATAFUCHI Toshihiro KYUSHU UNIV., DEPT.OF PHYSIOL.ASSISTANT, 医学部, 講師 (80177401)
AOU Shuji KYUSHU UNIV., DEPT.OF PHYSIOL.ASSOCIATE, 医学部, 助教授 (40150908)
ECKHART Simon MAX-PLANCK INSTITUTE,PROFESSOR
ECKHART Simo マックスブランク生理学臨床研究所, 教授
武 幸子 九州大学, 医学部, 助手 (80253425)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | antisense / thermoregulation / quantitative RT-PCR / hypothalamus / stress / the brain-gut-liver-immune axis / enteric flora / cytokines / 定量化RT-PCR / 海馬 / 記憶 / プロスタグランディン / インターフェロンα / インターロイキン6 / 肝門脈 / CRF類縁ペプタイド |
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| Research Abstract |
In this project, we are going to clarify the mechanisms how the neuroimmuno-endocrine network funcations as the host-defense system against the environmental stress. What we found in this project is as follows ; 1) Interleukin-6 inhibits long-term potentiotion in rat hippocampal neurons. 2) Tumor necrosis factor alpha not beta suppressed neuronal activity in the ventromedial hypothalamic neurons in vitro. 3) The mRNA of interferon alpha in the brain increased during immobilization stress. The medial preoptic area (MPO), which is the most potent acting site of IFN alpha, is involved in the central regulation of immunity by its suppressive influence on the splenic sympathetic nervous activity. 4) The c-fos protein expressed in the POA during hyper and hypothermic condition. Microinjection of antisense oligonucreotide for c-fos into the POA decreased body temperature. 5) Both IL-1 beta mRNA tissue content in the hypothalamus, the pituitary, and the liver but not in the hippocampus and the spleen increased by immobilization stress for 30 min. 6) Delayd cell death in the CAI neurons induced by brain ischemia was protected by continuous infusion of PACAP either intothe brain or in to the jugular vein. Since IL-6 concentration in the CSF increased by continuous infusion of PACAP,the tropic effect of PACAP on neurons might be, at least partly, mediated by brain cytokines. 7) The IM-induced IL-6 increase is completely abolished by in vivo neutralization of LPS.8) The concentration of LPS in the hepatoportal vein increases during IM.9) A fluorescent dye (FITC)-labeled LPS injected into the intestinal lumen is detected in Kupffer cells and sinusoidal endothelial cells after IM,78% of which are also stained with an anti-IL-6 antibody. The results suggest the presence of a brain-gut-liver immune axis, which is activated during pschophysical stresses.
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