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Analysis of sex differences in response to stress by use of model experimental animals for psychosomatic diseases

Research Project

Project/Area Number 17590600
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General internal medicine (including Psychosomatic medicine)
Research InstitutionWakayama Medical University

Principal Investigator

上山 敬司  Wakayama Medical University, 医学部, 准教授 (50264875)

Co-Investigator(Kenkyū-buntansha) HANO Takuzo  和歌山県立医科大学, 医学部, 教授 (90156381)
TSURUO Yoshihiro  和歌山県立医科大学, 医学部, 教授 (90207449)
KAWABE Tetsuya  和歌山県立医科大学, 医学部, 助教 (60508034)
清水 靖仁  和歌山県立医科大学, 医学部, 助教授 (80235671)
Project Period (FY) 2005 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywords性ホルモン / 情動的ストレス / 遺伝子発現 / たこつぼ型心筋症 / 動物モデル / エストロゲン受容体 / アンドロゲン受容体 / 酸化的ストレス / 男性更年期 / 性差 / 交感神経-副腎髄質
Research Abstract

ストレス応答における性差を性ホルモンレベルの変化から解明するため、エストロゲンとアンドロゲンの効果を検証した。 たこつぼ型心筋症は閉経後の女性に好発し、著しい性差がある。我々は不動化ストレス負荷を負荷したラットはたこつぼ型心筋症の動物モデルに成り得ること、エストロゲンの慢性投与でこの収縮不全が改善することを示した。エストロゲンの作用機序を脳、副腎、心臓で解析した。エストロゲン補充により、辺縁系→視床下部→副腎→心臓の各レベルでストレス応答が低下したが、心臓における心血管系保護物質の発現が増加した。エストロゲンは自律神経系を介する間接作用、および心臓への直接作用により、情動的ストレスに対して心保護効果を示す。
男性においても加齢に伴うアンドロゲンの減少による男性更年期が注目されているが、アンドロゲンレベルの変化も中枢神経系でのストレス応答を修飾することが示唆された。またオスの心臓においても、エストロゲンは心血管系保護物質を増加させることでストレスによる心機能不全を改善することを見出した。

Report

(5 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (61 results)

All 2009 2008 2007 2006 2005

All Journal Article (33 results) (of which Peer Reviewed: 14 results) Presentation (27 results) Book (1 results)

  • [Journal Article] Up-regulation of hemeoxygenase 1 in an animal model of takotsubo cardiomyopathy2009

    • Author(s)
      Ueyama T, Kawabe T, Hano T, Tsuruo Y, Ueda K, Ichinose M, Kimura H, Yoshida K
    • Journal Title

      Circ J (in press)

    • NAID

      10026904800

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] たこつぼ心筋症とその動物モデル2009

    • Author(s)
      上山敬司, 石蔵文信
    • Journal Title

      心身医学 (印刷中)

    • Related Report
      2008 Final Research Report
  • [Journal Article] 自律神経の中枢神経回路の解析2009

    • Author(s)
      上山敬司
    • Journal Title

      自律神経 (印刷中)

    • NAID

      10025570965

    • Related Report
      2008 Final Research Report
  • [Journal Article] 情動的ストレスよる、心臓での酸化ストレス2009

    • Author(s)
      上山敬司, 鶴尾吉宏
    • Journal Title

      自律神経 (印刷中)

    • Related Report
      2008 Final Research Report
  • [Journal Article] たこつぼ型心筋症の機序-動物実験からの新規視点2009

    • Author(s)
      上山敬司
    • Journal Title

      循環器科 (印刷中)

    • Related Report
      2008 Final Research Report
  • [Journal Article] Takotsubo Cardiomyopathy : A New Form of Acute, Reversible HeartFailure2008

    • Author(s)
      Akashi YJ, Goldstein DS, Barbaro G, Ueyama T
    • Journal Title

      Circulation 118

      Pages: 2754-2762

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Catecholamines and estrogen are involved in the pathogenesis of emotional stress-induced acute heart attack2008

    • Author(s)
      Ueyama T, Kasamatsu K, Hano T, Tsuruo Y, Ishikura F
    • Journal Title

      Ann NY Acad Sci 1148

      Pages: 479-480

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of estrogen on stress-induced activation of peptide neurons in PVN of overiectomized rats2008

    • Author(s)
      Kohno T , Hara Y, Takamata A, Ueyama T, Morimoto K
    • Journal Title

      Ann NY Acad Sci 1148

      Pages: 99-105

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Estrogen replacement suppress pressor response and oxidative stress induced by cage-switch stress in ovariectomized rats2008

    • Author(s)
      Morimoto K, Uji M, Ueyama T, Kimura H, Kohno T, Takamata A, Yano S, Yoshida K
    • Journal Title

      Ann NY Acad Sci 1148

      Pages: 213-218

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] .Adaptive HNE-Nrf2-HO1 pathway against oxidative stress is associated with acute gastric mucosal lesions.2008

    • Author(s)
      Ueda K, Ueyama T, Yoshida K, Kimura H, Ito T, Shimizu Y, Oka M, Tsuruo Y, Ichinose M
    • Journal Title

      Am J Physiol 295

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] 中枢の自律神経回路2008

    • Author(s)
      上山敬司, 仙波恵美子
    • Journal Title

      神経内科 68

      Pages: 235-244

    • Related Report
      2008 Final Research Report
  • [Journal Article] エストロゲンは心血管系と神経系とに作用し、情動的ストレスとカテコラミンで誘発される急性心不全を改善する2008

    • Author(s)
      上山敬司, 鶴尾吉宏, 石蔵文信
    • Journal Title

      自律神経 45

      Pages: 98-100

    • NAID

      10024485896

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Takotsubo Cardiomyopathy : A New Form of Acute, Reversible Heart Failure.2008

    • Author(s)
      Akashi YJ, Ueyama T, et al
    • Journal Title

      Circulation 118

      Pages: 2754-2762

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Catecholamines and estrogen are involved in the pathogenesis of emotional stress-induced acute heart attack.2008

    • Author(s)
      Ueyama T, et al
    • Journal Title

      Ann NY Acad Sci 1148:479-480, 2008 1148

      Pages: 479-480

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adaptive HNE-Nrf2-HO1 pathway against oxidative stress is associated with a cute gastric mucosal lesions.2008

    • Author(s)
      Ueda K. Ueyama T., et al.
    • Journal Title

      Am J Physiol 295 :, 2008. 295

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic estrogen supplementation following ovariectomy improves the emotional stress-induced cardiovascular responses by indirect action on the nervous system and by direct action on the heart2007

    • Author(s)
      Ueyama T, Ishikura F, Matsuda A, Asanuma T, Ueda K, Ichinose M, Kasamatsu K, Hano T, Akasaka T, Tsuruo Y, Morimoto K, Beppu S
    • Journal Title

      Circ J 71

      Pages: 565-573

    • NAID

      110006272149

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chronic estrogen supplementation following ovariectomy improves the emotional stress-induced cardiovascular responses by indirect action on the nervous system and by direct action on the heart.2007

    • Author(s)
      Ueyama T, et. al.
    • Journal Title

      Circ J 71

      Pages: 565-573

    • NAID

      110006272149

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] たこつぼ心筋症の原因解明2007

    • Author(s)
      上山 敬司
    • Journal Title

      Medical Technology 35

      Pages: 785-786

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Estrogen alters c-Fos response to immobilization stress in the brain of ovariectomized rats2006

    • Author(s)
      Ueyama T, Tanioku T, Nuta J, Kujira K, Ito T, Nakai S, Tsuruo Y
    • Journal Title

      Brain Res 1084

      Pages: 67-79

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] 卵巣摘除後のエストロゲン補充により、脳でのストレス応答が抑制される2006

    • Author(s)
      上山敬司、鶴尾吉宏
    • Journal Title

      自律神経 43

      Pages: 398-401

    • NAID

      10018449402

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] たこつぼ心筋症の神経解剖学的解析2006

    • Author(s)
      上山敬司、Loewy AD
    • Journal Title

      The Circulation Frontier 10

      Pages: 28-34

    • Related Report
      2008 Final Research Report
  • [Journal Article] Estrogen alters c-Fos response to immobilization stress in the brain of ovariectomized rats.2006

    • Author(s)
      Urysms Y et al.
    • Journal Title

      Brain Res 1084

      Pages: 67-79

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 左椎骨動脈の走行異常の一例.2006

    • Author(s)
      上山敬司, 他
    • Journal Title

      和歌山医学 57

      Pages: 8-10

    • NAID

      40015134256

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 卵巣摘除のエストロゲン補充により、脳でのストレス応答が抑制される.2006

    • Author(s)
      上山敬司, 他
    • Journal Title

      自律神経 43

      Pages: 398-401

    • Related Report
      2006 Annual Research Report
  • [Journal Article] たこつぼ心筋症の神経解剖学的解析.2006

    • Author(s)
      上山敬司, 他
    • Journal Title

      The Circulation Frontier 10

      Pages: 28-34

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cyclooxygenase 2 expression in rat corneas after ethanol exposure.2006

    • Author(s)
      Miyamoto T, et al.
    • Journal Title

      J Cataract Refract Surg 32

      Pages: 2736-1740

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Persistent median artery in the hand : A report with a brief reviev of the literature.2006

    • Author(s)
      Tsuro T, et al.
    • Journal Title

      Anat Sci Int 81

      Pages: 242-252

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 心疾患における情動的ストレスと自律神経の関与2005

    • Author(s)
      上山敬司 他
    • Journal Title

      自律神経 42

      Pages: 106-112

    • NAID

      10016687683

    • Related Report
      2005 Annual Research Report
  • [Journal Article] No Involvement of NGF Gene Locus in Hypertension in Spontaneously Hypertensive Rats.2005

    • Author(s)
      Nemoto K et al.
    • Journal Title

      Hypertens Res 28

      Pages: 155-163

    • Related Report
      2005 Annual Research Report
  • [Journal Article] STATE6 deficiency inhibits tubolointerstitial fibrosis in obstructive nephropathy.2005

    • Author(s)
      Yukawa K et al.
    • Journal Title

      Int J Mol Med 15

      Pages: 2205-2230

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The kinase domain of death-associated protein kinase is inhibitory for tubulointerstitial fibrosis in chronic obstructive nephopa2005

    • Author(s)
      Yukawa K et al.
    • Journal Title

      Int J Mol Med 15

      Pages: 73-78

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Sernaphorin 4A induces growth cone collapse of hippocampal neurons in a Rho/Rho-kinase-dependent manner.2005

    • Author(s)
      Yukawa K et al.
    • Journal Title

      Int J Mol Med 16

      Pages: 115-118

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Transcriptional activation in lens epithelial cells following an ocular blunt trauma.2005

    • Author(s)
      Shirai K et al.
    • Journal Title

      J Cataract Refract Sung 31

      Pages: 1226-1230

    • Related Report
      2005 Annual Research Report
  • [Presentation] Preventive effects of estrogen and beta blocker on stress-induced cardiac dysfunction in an experimental rat model2009

    • Author(s)
      石蔵文信、上山敬司
    • Organizer
      第73回日本循環器学会総会
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] Up-regulation of cyclooxygenase 2 in an Animal Model of Takotsubo Cardiomyopathy2009

    • Author(s)
      上山敬司, 川辺哲也,羽野卓三, 吉田謙一
    • Organizer
      第73回日本循環器学会総会
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] Takotsubo cardiomyopathy : a form of severe, reversible heart failure evoked by emotional distress in post-menopausal women.2008

    • Author(s)
      Uevama T. Akashi YJ
    • Organizer
      Ist International Symposium on Cardiac Sympathetic Neuroimaging.
    • Place of Presentation
      Kauai, Hawaii, USA.
    • Year and Date
      2008-10-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] たこつぼ心筋モデルにおける、ヘムオキシゲナーゼの増加2008

    • Author(s)
      上山敬司, 鶴尾吉宏
    • Organizer
      第61回日本自律神経学会総会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] 中枢の自律神経回路2008

    • Author(s)
      上山敬司
    • Organizer
      第61回日本自律神経学会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] Takotsubo cardiomyopathy : a form of severe, reversible heart failure evoked by emotional distress in post-menopausal women2008

    • Author(s)
      Ueyama T, Akashi YJ
    • Organizer
      First International Symposium on Cardiac Sympathetic Neuroimaging, 10Kauai
    • Place of Presentation
      Hawaii, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Up-regulation of hemeoxygenase 1 in an animal model of takotsubo cardiomyopathy2008

    • Author(s)
      Ueyama T, Yoshida K, Kimura H
    • Organizer
      19th International Symposium on the Autonomic Nervous System
    • Place of Presentation
      Kauai, Hawaii,USA
    • Related Report
      2008 Final Research Report
  • [Presentation] たこつぼ心筋症の実験的解析2008

    • Author(s)
      上山敬司, 石蔵文信
    • Organizer
      第49回日本心身医学会総会
    • Place of Presentation
      札幌
    • Related Report
      2008 Final Research Report
  • [Presentation] 情動的ストレス誘発心不全におけるヘムオキシゲナーゼの増加2008

    • Author(s)
      上山敬司, 伊藤隆雄, 鶴尾吉宏
    • Organizer
      第113回日本解剖学会総会
    • Place of Presentation
      大分
    • Related Report
      2008 Final Research Report
  • [Presentation] Up-regulation of Hemeoxygenase 1 in an Animal Model of Takotsubo Cardiomyopathy2008

    • Author(s)
      上山敬司, 笠松 謙, 吉田謙一
    • Organizer
      第72回日本循環器学会総会
    • Place of Presentation
      博多
    • Related Report
      2008 Final Research Report
  • [Presentation] Estrogen modulates the emotional stress-and catecholamine-induced acute heart failure.2007

    • Author(s)
      Ueyama T, et. al.
    • Organizer
      5^<th> congress of the international society for autonomic neuroscience
    • Place of Presentation
      Kyoto,Japan
    • Year and Date
      2007-10-20
    • Related Report
      2007 Annual Research Report
  • [Presentation] Catecholamine and estrogen are involved in the pathogenesis of stress-induced acute heart attack.2007

    • Author(s)
      Ueyama T, et. al.
    • Organizer
      9^<th> symposium on catecholamines and other neurotransmitters in stress
    • Place of Presentation
      Smolenice Castle,Slovakia
    • Year and Date
      2007-06-20
    • Related Report
      2007 Annual Research Report
  • [Presentation] Catecholamine and estrogen are involved in the pathogenesis of stress-induced acute heart attack.2007

    • Author(s)
      Ueyama T
    • Organizer
      第84回日本生理学会シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2007-03-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] Experimental findings of takotsubo disease.2007

    • Author(s)
      Ueyama T
    • Organizer
      第71回日本循環器学会ESC-JCS Joint Symposium
    • Place of Presentation
      神戸
    • Year and Date
      2007-03-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] Estrogen modulates the emotional stress- and catecholamine-induced acute heart failure2007

    • Author(s)
      Ueyama T, Tsuruo Y
    • Organizer
      5^<th>congress of the international society for autonomic neuroscience
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] Surge of catecholamines and reduction of estrogen trigger the emotional stress-induced acute cardiac dysfunction in human and in rat2007

    • Author(s)
      Ueyama T, Tsuruo Y, Akashi YJ
    • Organizer
      Satellite symposium of 5^<th> congress of the international society for autonomic neuroscience
    • Place of Presentation
      Wakayama, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] Catecholamine and estrogen are involved in the pathogenesis of stress-induced acute heart attack2007

    • Author(s)
      Ueyama T, Tsuruo Y, Ishikura F
    • Organizer
      9^<th> symposium on catecholamines and other neurotransmitters in stress
    • Place of Presentation
      Smolenice Castle, Slovakia
    • Related Report
      2008 Final Research Report
  • [Presentation] Experimental findings of takotsubo disease2007

    • Author(s)
      Ueyama T
    • Organizer
      第71回日本循環器学会学術集会ESC-JCS Joint Symposium
    • Place of Presentation
      神戸
    • Related Report
      2008 Final Research Report
  • [Presentation] Catecholamine and estrogen are involved in the pathogenesis of stress-induced acute heart attack2007

    • Author(s)
      Ueyama T
    • Organizer
      第84回日本生理学会大会シンポジウム
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] 情動的ストレスによるc-Fos 発現に対する去勢の影響2007

    • Author(s)
      上山敬司, 鯨和人, 川辺哲也, 伊藤隆雄, 鶴尾吉宏
    • Organizer
      第112回日本解剖学会総会
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Presentation] Castration alters c-Fos response to immobilization stress in the ratbrain2006

    • Author(s)
      上山敬司, 鯨和人, 川辺哲也, 伊藤隆雄, 鶴尾吉宏
    • Organizer
      第29回日本神経科学大会
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] Preconditioning stress could reduce the acute emotional stress-induced cardiac dysfunction in rats2006

    • Author(s)
      Matsuda A, Kitamoto M, Takeuchi H, Asanuma T, Ishikura F, Beppu S, Ueyama T
    • Organizer
      An echocardiographic study American Society of Echocardiography 17th Annual Scientific Sessions
    • Place of Presentation
      Baltimore, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Acute Preventing Effects of Arotinolol on Stress-induced hyperkinesis in a rat : Echocardiographic observation2006

    • Author(s)
      Matsuda A, Takeuchi H, Asanuma T, Ishikura F, Beppu S, Ueyama T
    • Organizer
      American Society of Echocardiography 17th Annual Scientific Sessions
    • Place of Presentation
      Baltimore, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] 情動的ストレスによる脳,副腎,心臓でのc-fos発現に対するエストロゲンの効果2006

    • Author(s)
      上山敬司, 伊藤隆雄, 仲井沙織, 鶴尾吉宏
    • Organizer
      第111回日本解剖学会総会
    • Place of Presentation
      相模原
    • Related Report
      2008 Final Research Report
  • [Presentation] Estrogen attenuates the emotional stress-induced activation of the sympathoadrenal-projecting central neurons in an animal model of takotsubo cardiomyopathy2006

    • Author(s)
      上山敬司, 笠松謙, 羽野卓三, 赤阪隆史, 石藏文信, 松田章子, 別府慎太郎
    • Organizer
      第70回日本循環器学会学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Final Research Report
  • [Presentation] 情動的ストレスに対するエストロゲンの脳、および心臓に対する効果-c-fos発現による検討2005

    • Author(s)
      上山敬司, 鶴尾吉宏, 羽野卓三, 石蔵文信, 松田章子, 別府慎太郎
    • Organizer
      第58回日本自律神経学会
    • Place of Presentation
      千葉
    • Related Report
      2008 Final Research Report
  • [Presentation] Estrogen alters c-Fos response to immobilization stress in the brain of ovariectomized rats2005

    • Author(s)
      上山敬司, 伊藤隆雄, 鶴尾吉宏
    • Organizer
      第28回日本神経科学大会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Book] 遺伝とストレス応答(p29-31)ストレスの事典、河野友信、石川俊編集2005

    • Author(s)
      上山敬司
    • Total Pages
      364
    • Publisher
      朝倉書店
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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