Project/Area Number |
10044332
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Research Category |
Grant-in-Aid for Scientific Research (B).
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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Research Institution | University of Occupational and Environmental Health |
Principal Investigator |
YAMASHITA Hiroshi University of Occupational and Environmental Health, School of Medicine, Department of Physiology, Professor, 医学部, 教授 (00030841)
|
Co-Investigator(Kenkyū-buntansha) |
INENAGA Kiyotoshi Kyushu Dental College, Department of Physiology, Professor, 歯学部, 教授 (90131903)
UETA Yoichi University of Occupational and Environmental Health, School of Medicine, Department of Physiology, Lecturer, 医学部, 講師 (10232745)
SHIBUYA Izumi University of Occupational and Environmental Health, School of Medicine, Department of Physiology, Associate Professor, 医学部, 助教授 (50162649)
寒川 賢治 国立循環器病センター, 生化学部, 部長 (00112417)
TRIBOLLET El ジュネーブ大学, 医学部, 講師
KOIZUMI Kiyo ニューヨーク州立大学, 医学部, 教授
KOW Lee Ming ロックフェラー大学, 神経生物&行動学, 助教授
VALE Wylie ソーク研究所, ペプチド生物学研究室, 教授
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
Keywords | Vasopressin / Adrenomedullin / Oxytocin / Orexin / Leptin / Urocortin / PACAP / アドレノメデユリン / 循環 / ペプチド / 視床下部 / 室傍核 / 視索上核 / イオンチャネル / 学習 |
Research Abstract |
The purpose of the present study was to investigate the role of cardiovascular-related peptides in the central nervous system (CNS), using genetic, molecular biological, morphological and physiological approaches. These approaches focused on the integrative investigation of the role from the genetics to behavior of cardiovascular-related peptides in the CNS. The examined cardiovascular-related peptides were vasopressin, adrenomedullin, orexin/hypocretin, leptin, TRH, CRH, urocortin and PACAP. (1) The expression of the vasopressin gene in the hypothalamus was upregulated in genetically polydipsic mice. (2) Adrenomedullin-like immunoreactive cells were distributed in the hypothalamic area, including the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of rats. Central administration of adrenomedullin selectively activated oxytocin-secreting neurons in the PVN and the SON with elevation of plasma oxytocin. (3) Orexin/hypocretin was newly discovered orexigenic peptides. Orexin-pr
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oducing neurons were localized in the lateral hypothalamic area. Their axons project to various regions in the CNS. Central administration of orexin selectively activated hypothalamo-pituitary adrenal axis in rats. Neonatal development of orexin in rats were examined. The expression of the orexin gene was markedly increased 15 and 20 days after birth. (4) The food deprivation induced down-regulation of neuronal nitric oxide synthase gene, TRH gene and CRH gene in the PVN were prevented by replacement with leptin. (5) The immunoreactivity of urocotin-producing cells and fibers in the SON was increased in the SON of hypertensive salt sensitive Dahl rats. (6) Central administration of PACAP activated vasopressin-secreting cells in the PVN and the SON and caused an increase in vasopressin heteronuclear RNA in the PVN and the SON. Kainic acid-induced seizure caused a marked induction of the PACAP gene in the parvocellular division of the PVN of rats. Furthermore, it is important to examine the role of cardiovascular-related peptides in the CNS. Less
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