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Common factor(s) involving vulnerability to stress and pathophysiology of depression in the elderly

Research Project

Project/Area Number 18590663
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 InstitutionNational Institute for Longevity Sciences,NCGG

Principal Investigator

MIZOGUCHI Kazushige  National Institute for Longevity Sciences,NCGG, 老年病研究部, 室長 (20416176)

Co-Investigator(Kenkyū-buntansha) 孫 楠  国立長寿医療センター, (研究所)・老年病研究部, 流動研究員 (60419900)
Co-Investigator(Renkei-kenkyūsha) IKEDA Ryuji  国立長寿医療センター(研究所), 老年病研究部, 流動研究員 (80463199)
SHOJI Hirotaka  国立長寿医療センター(研究所), 老年病研究部, 流動研究員 (00466278)
SUN Nan  国立長寿医療センター(研究所), 老年病研究部, 流動研究員 (60419900)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,960,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywords老化 / ストレス / 前頭前野 / うつ病 / ドーパミン / セロトニン / グルココルチコイド受容体 / ラット / 脳 / 視床下部-下垂体-副腎軸 / グルココルチコイド / 視床下部-下垂体-副腎皮質系
Research Abstract

実験動物(ラット)を用いた基礎研究において、老化の脳機能へ及ぼす影響を解析した。その結果、老化により、前頭前野のグルココルチコイド受容体(GR)が減少して、GRを介した反応が弱まると、前頭前野のドーパミンおよびセロトニンが減少することを見出した。そしてその結果、前頭前野そのものの機能低下としてワーキングメモリ障害や思考の柔軟性の低下が発生し、また一方で、このような前頭前野の機能低下がストレス脆弱性を形成すると考えられた。このように前頭前野のGRが、高齢者のうつ病やストレス脆弱性の発生機構に重要な役割を果たしている可能性が考えられた。

Report

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

    (27 results)

All 2009 2008 2007 Other

All Journal Article (22 results) (of which Peer Reviewed: 21 results) Presentation (3 results) Remarks (2 results)

  • [Journal Article] Saikokaryukotsuboreito, a herbal medicine, prevents chronic stress-induced anxiety in rats: comparison with diazepam2009

    • Author(s)
      Mizoguchi K, Ikeda R, Shoji H, Tanaka Y Jin XL, Kase Y, Takeda S, Maruyama W, Tabira T
    • Journal Title

      Nat. Med. (Tokyo) 63

      Pages: 69-74

    • NAID

      10025825655

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Saikokaryukotsuboreito, a herbal medicine, prevents chronic stress-induced anxiety in rats : comparison with diazepam2009

    • Author(s)
      Mizoguchi K., et al.
    • Journal Title

      Nat. Med. (Tokyo) 63

      Pages: 69-74

    • NAID

      10025825655

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Persistent depressive state after chronic stress in rats is accompanied by HPA axis dysregulation and reduced prefrontal dopamhergic neurotransmission2008

    • Author(s)
      Mizoguchi K, Shoji H, Ikeda R, Tanaka Y, Tabira T
    • Journal Title

      Pharmacol. Biochem. Behav. 91

      Pages: 170-175

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of glucocorticoid secretion induces a behaviorally depressive state in rotarod performance in rat2008

    • Author(s)
      Mizoguchi K, Ikeda R, Shoji H, Tanaka Y, Tabira T
    • Journal Title

      Pharmacol Biochem. Behav. 90

      Pages: 730-734

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of glucocorticoid secretion enhances cholinergic transmission in rat hippocampus2008

    • Author(s)
      Mizoguchi K, Shoji H, Ikeda R, Tanaka Y, Maruyama W, Tabira T
    • Journal Title

      Brain Res. Bull. 76

      Pages: 612-615

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aging attenuates glucocorticoid negative feedback in rat brain2008

    • Author(s)
      Mizoguchi K., et al.
    • Journal Title

      Neuroscience 159

      Pages: 270-259

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Persistent depressive state after chronic stress in rats is accompanied by HPA axis dysregulation and reduced prefrontal dopaminergic neurotransmission2008

    • Author(s)
      Mizoguchi K., et al.
    • Journal Title

      Pharmacol. Biochem. Behav. 91

      Pages: 170-175

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of glucocorticoid secretion induces a behaviorally depressive state in rotarod performance in rat2008

    • Author(s)
      Mizoguchi K., et al.
    • Journal Title

      Pharmacol. Biochem. Behav. 90

      Pages: 730-734

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of glucocorticoid secretion enhances cholinergic transmission in rat hippocampus2008

    • Author(s)
      Mizoguchi K., et al.
    • Journal Title

      Brain Res. Bull. 76

      Pages: 612-615

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of intracranial hypertension on cerebral hemorrhage induced autonomic nerve imbalance2007

    • Author(s)
      Jin XL, Jing W, Yan F, Zhang Z, Lu F, Jing S, Sun N, Mizoguchi K
    • Journal Title

      Neural Regen. Res. 2

      Pages: 175-178

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Saikokaryukotsuboreito, a herbal medicine, prevents chronic stress-induced dysfunction of glucocorticoid negative feedback system in rat brain2007

    • Author(s)
      Mizoguchi K, Sun N, Jin XL, Kase Y, Takeda S, Maruyama W, Tabira T
    • Journal Title

      Pharmacol. Biochem. Behav. 86

      Pages: 55-61

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Saikokaryukotsuboreito, a herbal medicine, prevents chronic stress-induced dysfunction of glucocorticoid negative feedback system in rat brain.2007

    • Author(s)
      Mizoguchi K., et. al.
    • Journal Title

      Pharmacol. Biochem. Behav. 86

      Pages: 55-61

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of intracranial hypertension on cerebral hemorrhage induced autonomic nerve imbalance.2007

    • Author(s)
      Jin XL., et. al.
    • Journal Title

      Neural. Regen. Res. 2

      Pages: 175-178

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiotensin-converting enzyme converts amyloid beta-protein 1-42(Abeta(1-42)) to Abeta(1-40), and its inhibition enhances brain Abeta deposition.2007

    • Author(s)
      Zou K., et. al.
    • Journal Title

      J. Neurosci. 27

      Pages: 8628-8635

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Saikokaryukotsuboreito, a herbal medicine, prevents chronic stress-induced dysfunction of glucocorticoid negative feedback system in rat brain.2007

    • Author(s)
      Mizoguchi K, Sun N, Jin XL, Kase Y, Takeda S, Maruyama W, Tabira T
    • Journal Title

      Pharmacol.Biochem.Behav. 86・1

      Pages: 55-61

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Age-related spatial working memory impairment is caused by prefrontal cortical dopaminergic dysfunction in rats

    • Author(s)
      Mizoguchi K, Ikeda R, Shoii H, Tanaka Y, Maruyama W, Tabira T
    • Journal Title

      Neuroscience (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Systemic disorders of calcium dynamics in rats with adenine-induced renal failure : implication for chronic kidney disease-related complications

    • Author(s)
      Ikeda R, Imai Y, Maruyama W, Mizoguchi K
    • Journal Title

      Nephrology (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hachimijiogan (Ba- Wei-Di-Huang- Wan), a herbal medicine, improves unbalance of calcium metabolism in aged rats

    • Author(s)
      Ikeda R, Mizoguchi K
    • Journal Title

      J. Ethnopharmacol. (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aging attenuates glucocorticoid negative feedback in rat brain

    • Author(s)
      Mizoguchi K, Ikeda R, Shoji H, Tanaka Y, Maruyama W, Tabira T
    • Journal Title

      Neuroscience 159

      Pages: 259-270

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Systemic disorders of calcium dynamics in rats with adenine-induced renal failure : implication for chronic kidney disease-related complications

    • Author(s)
      Ikeda R, Imai Y, Maruyama W, Mizoguchi K.
    • Journal Title

      Nephrology (印刷中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hachimijiogan (Ba-Wei-Di-Huang-Wan), a herbal medicine, improves unbalance of calcium metabolism in aged rats

    • Author(s)
      Ikeda R, Mizoguchi K.
    • Journal Title

      J. Ethnopharmacol (印刷中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of glucocorticoid secretion enhances cholinergic transmission in rat hippocampus.

    • Author(s)
      Mizoguchi K., et. al.
    • Journal Title

      Brain Res. Bull. (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 加齢による前頭前野の機能低下と漢方薬による改善作用(基礎)2008

    • Author(s)
      溝口和臣, 池田龍史, 昌子浩孝, 田中弥生, 丸山和佳子, 田平武
    • Organizer
      第8回抗加齢医学会総会(シンポジウム)
    • Place of Presentation
      東京
    • Year and Date
      2008-06-07
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] Angiotensin-converting enzyme converts Abetal-42 to Abetal-40 and its inhibition enhances brain Abeta deposition.2007

    • Author(s)
      Zou K., et. al.
    • Organizer
      第30回日本分子生物学会年会および第80回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-14
    • Related Report
      2007 Annual Research Report
  • [Presentation] 柴胡加竜骨牡蛎湯の抗うつ作用2007

    • Author(s)
      溝口和臣
    • Organizer
      第25回泌尿器科漢方研究会
    • Place of Presentation
      神戸
    • Year and Date
      2007-04-14
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.nils.go.jp/department/dgm/Mizoguchi-j.htm

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.nils.go.jp/department/dgm/Mizoguchi-j.htm

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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