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Modification of brain function regulating metabolism by antisense oligodeoxynucleotides

Research Project

Project/Area Number 07506004
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionThe University of Tokyo

Principal Investigator

TAKAHASHI Michio  The University of Tokyo, Graduate School of Agricultural and Life Science, Professor, 大学院・農学生命科学研究科, 教授 (30011943)

Co-Investigator(Kenkyū-buntansha) HORIKOSHI Hiroyoshi  Sankyo Co., Ltd., Biological Research Laboratories, Group Director, 生物研究所, 室長
MATSUYAMA Shigemi  The University of Tokyo, Graduate School of Agricultural and Life Science, Assis, 大学院・農学生命科学研究科, 助手 (80219526)
KAI Chieko  The University of Tokyo, Graduate School of Agricultural and Life Science, Assoc, 大学院・農学生命科学研究科, 助教授 (10167330)
MORI Yuji  The University of Tokyo, Graduate School of Agricultural and Life Science, Profe, 大学院・農学生命科学研究科, 教授 (40157871)
NISHIHARA Masugi  The University of Tokyo, Graduate School of Agricultural and Life Science, Assoc, 大学院・農学生命科学研究科, 助教授 (90145673)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 1997: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1996: ¥8,200,000 (Direct Cost: ¥8,200,000)
KeywordsAntisense oligodeoxynucleotides / Hypothalamus / Metabolism / Feeding behavior / Obesity / Running activity / gamma-aminobutyric acid / glutamic acid decarboxylase / γ-アミノ酪酸
Research Abstract

In the ventromedial nucleus of the hypothalamus (VMH), gamma-aminobutyric acid (GABA) plays an important role in regulating metabolism. The GABA synthetic enzyme, glutamic acid decarboxylase (GAD) consists of two isozymes, GAD65 and GAD67. In the present study, the effect of injection of antisense oligodeoxynucleotides (ODNs) to each GAD isozyme into the VMH of the male rat on food intake, body weight and locomotor activity was examined. Phosphorothioated antisense ODNs were incorporated in the water-absorbent polymer (WAP) and injected into bilateral VMH,and the day of injection was designated as day 0. Antisense ODNs to GAD65 and GAD67 tended to reduce food intake on day 1, though not significant. Simultaneous injection of antisense ODNs to both GAD isozymes significantly decreased food intake on only day 1, but body weight remained suppressed by this treatment for 5 days. On the other hand, simultaneous administration of antisense ODNs to GAD65 and GAD67 significantly increased loco … More motor activity between days 3-5, whcreas other treatments did not. This increase in daily locomotor activity was mainly due to the increase in locomotor activity during the light, but not dark, phase. Neither vehicle (WAP) nor control ODN affected food intake, body weight and locomotor activity. Histological studies indicated that, 24 h after the injection, antisense ODN distributed within about 800 mum from the edge of area where WAP was located and then gradually disappeared with days, but still remained within 300 mum distance even 7 days after the injection. Antisense ODN was effectively incorporated by all the cell types examined, i.e.neurons, astrocytes and microglias. Further, HPLC analysis revealed that antisense ODN to either GAD isozyme decreased the content of GABA,but not other amino acids, in the VMH by 24 h. These results suggest that either GAD isozyme is synergistically involved in enhancing food intake and suppressing locomotor activity in rat VMH.This study also indicates that central injection of antisense oligodeoxynucleotides is useful means to regulate animal metabolism. Less

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Bannai M: "Effect of injection of antisenseoligonucleotides of GAD isozymes into rat VMH on food intake and locomotor activity" Brain Research. (印刷中). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshida S: "A novel steroid inhibitor for a rat 20α-hydroxysteroid dehydrogenaseisozyme(HSDI)" Biology of Reproduction. 57. 1433-1437 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamanouchi K: "Inhibin α-subunit mRNA is expressed in the corpus luteum of the pregnant mare" Journal of Reproduction and Development. 43. 267-270 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ikeda A: "Different female reproductive phenotypes determined by human growth hormone(hGH) levels in hGH-transgenic rats" Biology of Reproduction. 56. 847-851 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoo MJ: "Involvement of prostaglandins insupperssion of gonadotropin-releasing hormone pulse generator activity by tumornecrosis factor-α" Journal of Reproduction and Development. 43. 181-187 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoo MJ: "Tumor necrosis factor-α mediates endotoxin induced suppression of gonadotropin-releasing hormone pulse generator activity in the rat" Endocrine Journal. 44. 141-148 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suzuki M: "Reproductive Biology Update:Novel Tools for Assesment of Enviromental Toxicity" Miyamoto H,Manabe N(eds),Nakanishi Printing Co., 498 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nishihara M: "Neural Control of the Reproduction:Physiology and Behavior" Maeda K,Tsukamura H,Yokoyama A(eds),Karger, 254 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Bannai M,et al.: "Effect of injection of antisense oligonucleotides of GAD isozymes into rat VMH on food intake and locomotor activity" Brain research. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshida S,et al.: "A novel steroid inhibitor for a rat 20alpha-hydroxysteroid dehydrogenase isozyme (HSD1)" Biology of Reproduction. 57. 1433-1437 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamanouchi K,et al.: "Inhibin alpha-subunit mRNA is expressed in the corpus luteum of the pregnant mare" Journal of Reproduction and Development. 43. 267-270 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ikeda A,et al.: "Different female reproductive phenotypes determined by human growth hormone (hGH) levels in hGH-transgenic rats" Brology of Reproduction. 56. 847-851 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoo MJ,et al.: "Involvement of prostaglandins in suppression of gonadotropin-releasing hormone pulse generator activity by tumor necrosis factor-alpha" Journal of Reproduction and Development. 43. 181-187 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoo MJ,et al.: "Tumor necrosis factor-alpha mediates endotoxin induced suppression of gonadotropin-releasing hormone pulse generator activity in the rat" Endocrine Journal. 44. 141-148 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suzuki M,et al: Reproductive Biology Update : Novel Tools for Assesment of Enviromental Toxicity. Miyamoto H,Manabe N (eds), Nakanishi Printing Co., 498 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nishihara M,et al.: Neural Control of the Reproduction : Physiology and Behavior. Maeda K,Tsukamura H,Yokoyama A (eds), Karger, 254 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Bannai M: "Effect of injection of antisense oligonucleotides of GAD isozymes into rat VMH on food intake and locomotor activity" Brain Research. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshida S: "A novel steroid inhibitor for a rat 20α-hydroxysteroid dehydrogenase isozyme (HSD1)" Biology of Reproduction. 57. 1433-1437 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamanouchi K: "Inhibin α-subunit mRNA is expressed in the corpus luteum of the pregnant mare" Journal of Reproduction and Development. 43. 267-270 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ikeda A: "Different female reproductive phenotypes determined by human growth hormone (hGH) levels in hGH-transgenic rats" Biology of Reproduction. 56. 847-851 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoo MJ: "Involvement of prostaglandins in suppression of gonadotropin-releasing hormone pulse generator activity by tumor necrosis factor-α" Journal of Reproduction and Development. 43. 181-187 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoo MJ: "Tumor necrosis factor-α mediates endotoxin induced suppression of gonadotropin-releasing hormone pulse generator activity in the rat" Endocrine Journal. 44. 141-148 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suzuki M: "Reproductive Biology Update : Novel Tools for Assesment of Enviromental Toxicity" Miyamoto H, Manabe N (eds), Nakanishi Printing Co., 498 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nishihara M: "Neural Control of the Reproduction : Physiology and Behavior" Maeda K, Tsukamura H, Yokoyama A (eds), Karger, 254 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mi-Jeong Yoo: "Tumor necrosis factor-α mediates endotoxin induced suppression of gonadotropin-releasing hormone pulse generator activity in the rat" Endocrine Journal. 44. 141-148 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hirotaka Kanuka: "Prolactin expresses differential effect on apoptotic cell death of luteal cells in vivo and in vitro" Endocrine Journal. 44. 11-22 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shuichi Onami: "Splenic macrophages alter the steroidgenesis of Leydig cells in vitro" Endocrine Journal. 43. 477-485 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Michiru Hirasawa: "The rostral ventrolateral medulla mediates suppression of the circulatory system by the ventromedial nucleus of the hypothalamus" Brain Research. 724. 186-190 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fusae Nishimura: "Changes in chemical sensitivity of rat ventromedial hypothalamic neurons by food deprivation" Physiology & Behaviour. 60. 7-12 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Michiru Hirasawa: "Neural activity in the VMH associated with suppression of the circulatory system in rats" Physiology & Behaviour. 59. 1017-1023 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Masugi Nishihara: "Neural Control of the Reproduction:Physiology and Behavior" Yokoyama A(ed),Japan Scientific Societis Press(in press), (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 高橋迪雄: "ヒューマン・サイエンス:生殖機能と下垂体前葉機能調節系" コロナ社(印刷中), (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hirasawa M 他: "The rostral ventrolateral medulla mediates suppression of the circulatory system by the ventromedial nucleus of the hypothalamus" Brain Research. (印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nishimura F 他: "Changes in chemical sensitivity of rat ventromedial hypothalamic neurons by food deprivation" Physiology & Behavior. (印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hirasawa M 他: "Neural activity in the VMH associated with suppression of the circulatory system in rats" Physiology & Behavior. (印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nishimura F 他: "Excitability of neurons in the ventromedial nucleus in rat hypothalamic slices: Modulation by amino acids at cerebrospinal fluid levels" Brain Research. 691. 217-222 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Suzuki M 他: "Hypothalamic gonadotropin-releasing hormone gene expression during rat estrous cycle" Endocrine Journal. 42. 789-796 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamanouchi K 他: "Molecular cloning of cDNA for inhibin α-subunit from equine ovary" The Journal of Veterinary Medical Science. 57. 905-909 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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