Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants |
Environmental physiology (including Physical medicine and Nutritional physiology)
|Research Institution||Kyoto University |
MATSUMURA Kiyoshi Kyoto Univ., Grad. Sch. Informatics, Associate professor, 情報学研究科, 助教授 (10157349)
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)
白木 琢磨 京都大学, 情報学研究科, 助手 (10311747)
|Project Period (FY)
2001 – 2003
Completed (Fiscal Year 2003)
|Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥7,900,000 (Direct Cost: ¥7,900,000)
|Keywords||prostaglandin E synthase / cyclooxygenase / fever / brain endothelial cells / medullary raphe nucleus / brown adipose tissue / prostaglandin receptor / GABA / プロスタグランジン / ホスホリパーゼA2 / プロスタグランジン輸送体 / くも膜 / シクロオキシゲナーゼ-2 / 血管内皮細胞 / 縫線核 / EP3受容体 / PGE合成酵素|
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
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