Evaluation of oxidative stress in the brain of a mouse model of Alzheimer disease by in vivo EPR imaging system.

• Project/Area Number: 26861008
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Sapporo Medical University
• Principal Investigator: Emoto Miho 札幌医科大学, 医療人育成センター, 研究員 (10578735)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: EPRイメージング / アルツハイマー病モデルマウス / 酸化ストレス / エイジング / EPRイメージング法 / レドックスバランス

Outline of Final Research Achievements

Alzheimer’s disease (AD) is a neurodegenerative disease clinically characterized by progressive cognitive dysfunction. Deposition of amyloid-β (Aβ) peptides is the most important pathophysiological hallmark of AD. Oxidative stress induced by reactive oxygen species (ROS) is prominent in AD, and several reports suggest the relationship between the change in redox status and AD pathology containing progressive Aβ deposition.
electron paramagnetic resonance (EPR) imaging is used to acquire spatial information about the distribution of free radical species in vivo and visualize oxidative stress derived from ROS.
in vivo changes in redox status with age in both wild-type (WT) and AD mouse brains were measured noninvasively by three-dimensional (3D) EPR imaging using nitroxide (MCP) as a redox-sensitive probe. EPR imaging clearly visualized the accelerated change in redox status of AD mouse brain compared with WT.

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
• [Journal Article] Brain imaging in methamphetamine-treated mice using a nitroxide contrast agent for EPR imaging of the redox status and a gadolinium contrast agent for MRI observation of blood-brain barrier function. (2015)
  • Author(s): Emoto MC, Yamato M, Sato-Akaba H, Yamada K, Matsuoka Y, Fujii HG.
  • Journal Title: Free Radical Research Volume: 49 Issue: 8 Pages: 1038-1047
  • DOI: 10.3109/10715762.2015.1040787
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Brain redox imaging in the pentylenetetrazole (PTZ)-induced kindling model of epilepsy by using in vivo electron paramagnetic resonance and a nitroxide imaging probe. (2015)
  • Author(s): Emoto CM, Yamato M, Sato-Akaba H, Yamada K, Fujii GH.
  • Journal Title: Neuroscience Letters Volume: 608 Pages: 40-44
  • DOI: 10.1016/j.neulet.2015.10.008
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Dynamic changes in the distribution and time course of blood-brain barrier-permeative nitroxides in the mouse head with EPR imaging: visualization of blood flow in a mouse model of ischemia. (2014)
  • Author(s): Emoto MC, Sato-Akaba H, Hirata H, Fujii HG.
  • Journal Title: Free Radical Biology and Medicine Volume: 74 Pages: 222-228
  • DOI: 10.1016/j.freeradbiomed.2014.06.026
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Synthesis of ^<15>N-labeled 4-oxo-2,2, 6,6-tetraethylpiperidine nitroxide for EPR brain imaging (2014)
  • Author(s): Xiaolei Wang, Miho Emoto, Atsushi Sugimoto, Yusuke Miyake, Kaori Itto, Mitsuo Amasaka, Shu Xu, Hiroshi Hirata, Hirotada Fuji, Hirokazu Arimoto
  • Journal Title: Tetrahedron Letters Volume: 55 Issue: 13 Pages: 2146-2149
  • DOI: 10.1016/j.tetlet.2014.02.063
  • Peer Reviewed
• [Journal Article] The Effect of Aging for Oxidative Stress in Mouse Brains by EPR Imaging Method. (2014)
  • Author(s): Miho C Emoto, Akihiro Matsumura, Hiromi Suzuki, Shun Shimohama, Hirotada G Fujii.
  • Journal Title: Free Radical Biology and Medicine Volume: 76 Pages: S22-S23
  • DOI: 10.1016/j.freeradbiomed.2014.10.472
  • Peer Reviewed
• [Presentation] Novel theranostics work as therapeuic drug and imaging probe for MRI and EPR imaging (2015)
  • Author(s): M.C. Emoto, S Sato, H.G. Fujii
  • Organizer: ESMRMB2015
  • Place of Presentation: エジンバラ、イギリス
  • Year and Date: 2015-10-01
  • Int'l Joint Research
• [Presentation] 抗炎症薬とニトロキシド化合物によるTheranosticsイメージングプローブの開発 (2015)
  • Author(s): 江本美穂、佐藤慎吾、藤井博匡
  • Organizer: 第43回日本磁気共鳴医学会大会
  • Place of Presentation: 東京ドームホテル(東京都文京区)
  • Year and Date: 2015-09-10
• [Presentation] Development of Theranostics Imaging Probe for MRI and EPR Imaging (2015)
  • Author(s): Emoto Miho, Sato Shingo, Fujii Hirotada G.
  • Organizer: 第23回国際磁気共鳴医学会
  • Place of Presentation: トロント、カナダ
  • Year and Date: 2015-05-01
  • Int'l Joint Research
• [Presentation] The Effect of Aging for Oxidative Stress in Mouse Brains by EPR Imaging Method. (2014)
  • Author(s): Miho C Emoto, Akihiro Matsumura, Hiromi Suzuki, Shun Shimohama, And Hirotada G Fujii.
  • Organizer: 第21回米国フリーラジカル生物医学会議
  • Place of Presentation: シアトル・アメリカ合衆国
  • Year and Date: 2014-11-19 – 2014-11-23
• [Presentation] MRIを用いたアスコルビン酸耐性ニトロキシド化合物TEEPONEのマウス頭部における動態解析 (2014)
  • Author(s): 江本美穂、山田健一、大和真由美、藤井博匡
  • Organizer: 第42回日本磁気共鳴医学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-09-18 – 2014-09-20
• [Presentation] Co-registered EPR and MRI of the mouse head indicates detailed distributions of piperidine nitroxides. (2014)
  • Author(s): MC Emoto, H Sato-Akaba, H Hirata, HG Fujii.
  • Organizer: 第22回国際磁気共鳴医学会
  • Place of Presentation: ミラノ・イタリア
  • Year and Date: 2014-05-10 – 2014-05-16