Molecular Analysis of cognitive impairment associated with postmenopausal memory loss and Alzheimer's disease

• Project/Area Number: 20590083
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Osaka University
• Principal Investigator: TAKUMA Kazuhiro Osaka University, 大学院・薬学研究科, 准教授 (90289025)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: アルツハイマー病 / 更年期障害 / エストロゲン / 海馬 / ミトコンドリア / コリン作動性神経系 / 神経変性

Research Abstract

Estrogen decline after menopause may influence cognitive performance and increase risk for Alzheimer's disease (AD) in women. We have previously found that combination of chronic stress and ovariectomy (OVX) causes memory impairment in mice. In this study, we found that cholinergic neuronal loss in the hippocampal CA3 region is involved in OVX/stress-induced memory impairment in mice, and donepezil and galantamine, which are clinically used for AD therapy, improved the memory impairment.

Research Products

• [Journal Article] Nicotine ameliorates impairment of working memory in methamphetamine-treated rats (2011)
  • Author(s): Hiroyuki Mizoguchi, Daisuke Ibi, Fumiaki Takase, Taku Nagai, Hiroyuki Kamei, Erika Toth, Jun Sato, Kazuhiro Takuma, Kiyofumi Yamada
  • Journal Title: Behav.Brain Res. 220(1) Pages: 159-163
• [Journal Article] Alterations of emotional and cognitive behaviors in matrix metalloproteinase-2 and-9-deficient mice (2011)
  • Author(s): Hiroyuki Mizoguchi
  • Journal Title: The Open Behavioral Science Journal Volume: 4 Pages: 19-25
  • Peer Reviewed
• [Journal Article] Nicotine ameliorates impairment of working memory in methamphetamine-treated rats. (2011)
  • Author(s): Hiroyuki Mizoguchi
  • Journal Title: Behavioural Brain Research Volume: 220 Pages: 159-163
  • Peer Reviewed
• [Journal Article] Alterations of emotional and cognitive behaviors in matrix metalloproteinase-2 and -9-deficient mice (2010)
  • Author(s): Hiroyuki Mizoguchi, Daisuke Ibi, Kazuhiro Takuma, Erika Toth, Jun Sato, Shigeyoshi Itohara, Toshitaka Nabeshima, Kiyofumi Yamada
  • Journal Title: Open Behav.Sci.J. 4 Pages: 19-25
• [Journal Article] Aβトランスポーター (2010)
  • Author(s): 田熊一敞 片岡駿介, 吾郷由希夫, 松田敏夫
  • Journal Title: 脳21 13 Pages: 59-62
• [Journal Article] Aβトランスポーター (2010)
  • Author(s): 田熊, 一敞(一浩)
  • Journal Title: 脳21 13 Pages: 59-62
• [Journal Article] RAGE-mediated signaling contributes to intraneuronal transport of amyloid-β and neuronal dysfunction (2009)
  • Author(s): Kazuhiro Takuma, Fang Fang, Wensheng Zhang, Shiqiang Yan, Emiko Fukuzaki, Heng Du, Alexander Sosunov, Guy McKhann, Yoko Funatsu, Noritaka Nakamichi, Taku Nagai, Hiroyuki Mizoguchi, Daisuke Ibi, Osamu Hori, Satoshi Ogawa, David M.Stern, Kiyofumi Yamada, Shirley ShiDu Yan
  • Journal Title: Proc.Natl.Acad.Sci.USA 106(47) Pages: 20021-20026
• [Journal Article] ミトコンドリア障害と神経系のアポトーシス～アルツハイマー病解明へのアプローチ～ (2009)
  • Author(s): 田熊一敞, 片岡駿介, 吾郷由希夫, 松田敏夫
  • Journal Title: 日本薬理学雑誌 134(4) Pages: 180-183
  • NAID: 10025741619
• [Journal Article] Matrix metalloprotease-9 inhibition improves amyloid β-mediated cognitive impairment and neurotoxicity in mice (2009)
  • Author(s): Hiroyuki Mizoguchi, Kazuhiro Takuma, Emiko Fukuzaki, Daisuke Ibi, Eiichi Someya, Ko-hei Akazawa, Tursun Alkam, Hiroko Tsunekawa, Akihiro Mouri, Yukihiro Noda, Toshitaka Nabeshima, Kiyofumi Yamada
  • Journal Title: J.Pharmacol.Exp.Ther. 331(1) Pages: 14-22
• [Journal Article] RAGE-mediated signaling contributes to intraneuronal transport of amyloid-β and neuronal dysfunction (2009)
  • Author(s): TAKUMA, Kazuhiro
  • Journal Title: Proc.Natl.Acad.Sci.USA 106 Pages: 20021-20026
  • Peer Reviewed
• [Journal Article] Matrix metalloprotease-9 inhibition improves amyloid β-mediated cognitive impairment and neurotoxicity in mice (2009)
  • Author(s): MIZOGUCHI, Hiroyuki
  • Journal Title: J.Pharmacol.Exp.Ther. 331 Pages: 14-22
  • Peer Reviewed
• [Journal Article] ミトコンドリア障害と神経系のアポトーシス～アルツハイマー病解明へのアプローチ～ (2009)
  • Author(s): 田熊, 一敞(一浩)
  • Journal Title: 日本薬理学雑誌 134 Pages: 180-183
  • NAID: 10025741619
• [Journal Article] Ovariectomy increases serum amyloid β peptide and hippocampal ABAD levels in mice (2008)
  • Author(s): Emiko Fukuzaki, Kazuhiro Takuma, Yoko Funatsu, Yukiko Himeno, Yuko Kitahara, Hiroyuki Mizoguchi, Daisuke Ibi, Koji Koike, Masaki Inoue, Shi Du Yan, Kiyofumi Yamada
  • Journal Title: Nuerochem.Int. 52(7) Pages: 1358-1364
• [Journal Article] Ovariectomy increases neuronal amyloid-βbinding alcoholdehydrogenase level in the mouse hippocampus (2008)
  • Author(s): FUKUZAKI, Emiko
  • Journal Title: Neurochem. Int. 52 Pages: 1358-1364
  • Peer Reviewed
• [Presentation] 糖化最終産物受容体を介するアミロイド神経毒性発現とその薬物標的としての可能性 (2011)
  • Author(s): 田熊一敞, 松田敏夫, 山田清文
  • Organizer: 第84回日本薬理学会年会シンポジウム
  • Place of Presentation: 大会中止のため誌上開催
  • Year and Date: 2011-02-15
• [Presentation] Receptor for advanced glycation endproducts : a potential target for amyloid-β peptide-mediated neuropathology. (2011)
  • Author(s): Kazuhiro Takuma
  • Organizer: 第84回日本薬理学会年会シンポジウム
  • Place of Presentation: 大会中止のため誌上開催(招待講演)
  • Year and Date: 2011-02-15
• [Presentation] Mitochondria-mediated neurotoxicity in Alzheimer's disease. (2010)
  • Author(s): 田熊一敞, 松田敏夫
  • Organizer: 第37回日本トキシコロジー学会学術年会シンポジウム
  • Place of Presentation: 沖縄コンベンションセンター
  • Year and Date: 2010-06-17
• [Presentation] Mitochondria-mediated neurotoxicity in Alzheimer's disease. (2010)
  • Author(s): Kazuhiro Takuma
  • Organizer: 第37回日本トキシコロジー学会学術年会シンポジウム
  • Place of Presentation: 沖縄県 沖縄コンベンションセンター(招待講演)
  • Year and Date: 2010-06-17
• [Presentation] ミトコンドリア障害と神経系のアポトーシス ～アルツハイマー病解明へのアプローチ～ (2009)
  • Author(s): 田熊一敞, 片岡駿介, 吾郷由希夫, 松田敏夫
  • Organizer: 第82回日本薬理学会年会シンポジウム
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-03-16
• [Presentation] ミトコンドリア障害と神経系のアポトーシス 〜アルツハイマー病解明へのアプローチ〜 (2009)
  • Author(s): 田熊, 一敞(一浩)
  • Organizer: 第82回日本薬理学会年会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2009-03-16
• [Presentation] Role of receptor for advanced glycation endproducts in neuronal amyloid β-peptide membrane transport (2008)
  • Author(s): Kazuhiro Takuma, Emiko Fukuzaki, Yoko Funatsu, David M.Stern, 山田清文, Shi Du Yan
  • Organizer: Alzheimer's Association International Conference on Alzheimer's Disease (ICAD2008)
  • Place of Presentation: McCormick Place, Chicago, IL, USA.
  • Year and Date: 2008-07-30
• [Presentation] Role of receptor for advanced glycation endproducts inneuronal amyloid β-peptide membrane transport (2008)
  • Author(s): TAKUMA, Kazuhiro
  • Organizer: The Alzheimer's Association 2008 International Conference on Alzheimer's Disease (ICAD2008)
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2008-07-30
• [Remarks]
  • URL: http://www.phs.osaka-u.ac.jp/homepage/b013/
• [Remarks]
  • URL: http://www.phs.osaka-u.ac.jp/homepage/b013/
• [Remarks]
  • URL: http://www.phs.osaka-u.ac.jp/homepage/b013/