Evaluation of oxidative stress and elucidation of pathogenesis in Alzheimer disease by in vivo electron paramagnetic resonance imaging

• Project/Area Number: 15K19288
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Sapporo Medical University
• Principal Investigator: Matsumura Akihiro 札幌医科大学, 医学部, 助教 (20464498)
• Research Collaborator: FUJII Hirotada
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: アルツハイマー病 / アミロイドβ / トランスジェニック / 酸化ストレス / ROS / redox status / ミクログリア / ガランタミン

Outline of Final Research Achievements

The purpose of this study is to analyze the mechanism of Alzheimer disease (AD) and apply the result to new therapeutic strategy, by evaluating the change of oxidative stress, cognitive function and histopathology in the brain when therapeutic intervention was given to AD model animals. I used in vivo electron paramagnetic resonance (EPR) imaging in order to evaluate the oxidative stress in the brain of model animals. APPswe/PS1dE9 mice (AD mice) and their littermates (Wild mice) were orally dispensed 5mg/kg of galantamine or distilled water from very early stage (3 months of age) or from early stage (6 months of age) of AD.
The results of behavioral assessment by novel object recognition (NOR) test indicated the improvement in congnitive function. Aβ deposition in the cortex decreased in the galantamine-administered group compared with control group. EPR imaging tend to visualize the less oxidative stress in the galantamine treatment group.

Research Products

• [Journal Article] Evaluation of oxidative stress in the brain of a transgenic mouse model of Alzheimer disease by in vivo electron paramagnetic resonance imaging. (2015)
  • Author(s): Matsumura A, Emoto MC, Suzuki S, Iwahara N, Hisahara S, Kawamata J, Suzuki H,Yamauchi A, Sato-Akaba H, Fujii HG, Shimohama S.
  • Journal Title: Free Radic Biol Med. Volume: 85 Pages: 165-173
  • DOI: 10.1016/j.freeradbiomed.2015.04.013
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Temporal changes of the marker of microglial activation in APdE9 mice. (2016)
  • Author(s): 松村晃寛, 鈴木紘美, 藤倉 舞, 岩原直敏, 真部建郎, 松下隆司, 鈴木秀一郎, 久原 真, 川又 純, 下濱 俊
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2016-05-18
• [Presentation] APdE9マウスにおけるミクログリア内のマーカーの発現の経時的推移 (2015)
  • Author(s): 松村晃寛, 藤倉 舞, 岩原直敏, 真部建郎, 松下隆司, 鈴木秀一郎, 久原 真, 川又 純, 下濱 俊
  • Organizer: 第34回日本認知症学会学術集会
  • Place of Presentation: リンクステーションホール青森（ 青森県青森市）
  • Year and Date: 2015-10-02
• [Presentation] Temporal changes of microglial activatio and alpha7 nAChR in APdE9 mice. (2015)
  • Author(s): 松村晃寛, 鈴木紘美, 山内綾乃, 岩原直敏, 松下隆司, 鈴木秀一郎, 久原 真, 川又 純, 高田和幸, 北村佳久, 下濱 俊
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 新潟コンベンションセンター（ 朱鷺メッセ）（ 新潟県新潟市）
  • Year and Date: 2015-05-20