Imaging study of redox status in vivo in oxidative stress-associateddisease model animals using OMRI

2012 Fiscal Year Final Research Report

• Project/Area Number: 22249003
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Kyushu University
• Principal Investigator: UTSUMI Hideo 九州大学, 先端融合医療レドックスナビ研究拠点, 特任教授 (20101694)
• Co-Investigator(Kenkyū-buntansha): ICHIKAWA Kazuhiro 九州大学, 先端融合医療創成センター, 教授 (10271115) ; YAMADA Ken-ichi 九州大学, 薬学研究院, 准教授 (60346806) ; HYODO Fuminori 九州大学, 先端融合医療レドックスナビ研究拠点, 准教授 (10380693)
• Co-Investigator(Renkei-kenkyūsha): HIROOKA Yoshitaka 九州大学, 医学研究院, 教授 (90284497) ; YASUKAWA Keiji 九州大学, 薬学研究院, 助教 (80372738) ; YAMATO Mayumi 九州大学, 先端融合医療レドックスナビ研究拠点, 准教授 (30380695) ; KATO Takahiro 九州大学, 先端融合医療レドックスナビ研究拠点, 特任准教授 (70546465) ; NUTTAVUT Kosem 九州大学, 先端融合医療レドックスナビ研究拠点, 特任助教 (60532851)
• Project Period (FY): 2010 – 2012
• Keywords: 薬学 / 生物物理 / 生体分子 / 可視化

Research Abstract

Novel imaging technique Overhauser-MRI (OMRI) enables visualization of tissue redox status in animals based on dynamic nuclear polarization (DNP) with higher spatial resolution compared with electron spin resona nce imaging (ESRI). In this study, we applied OMRI to various oxidative disease models such as dopaminergic neurotoxicity , indomethacin-induced gastric damage and schizophrenic disorder. As a noninvasive technique, combining OMRI imaging with redox probes to monitor tissue redox status may be useful in acquiring valuable information regarding organ function for preclinical and clinical studies of oxidative diseases.

Research Products

• [Journal Article] Permeability Studies of Redox-Sensitive Nitroxyl Spin Probes Through Lipid Membranes Using an L-Band ESR Spectrometer. (2013)
  • Author(s): Benial AM, Dhas MK, Ichikawa K, Yamada KI, Hyodo F , Jawahar A, Utsumi H
  • Journal Title: Appl Magn Reson Volume: 44(4) Pages: 439-47
  • DOI: DOI:10.1007/s00723-012-0383-0
  • Peer Reviewed
• [Journal Article] Are microglia minding us? Digging up the unconscious mind-brain relationship from a neuropsychoanalytic approach (2013)
  • Author(s): Kato TA, Kanba S
  • Journal Title: Front Hum Neurosci Volume: 13
  • DOI: DOI:10.3389/fnhum.2013.00013
  • Peer Reviewed
• [Journal Article] Neurotransmitters,Psychotropic Drugs and Microglia: Clinical Implications for Psychiatry (2013)
  • Author(s): Kato TA, Yamauchi Y, Horikawa H, Monji A, Mizoguchi Y, Seki Y, Hayakawa K, Utsumi H, Kanba S
  • Journal Title: Curr Med Chem Volume: 20 (3) Pages: 331-44
  • URL: http://www.eurekaselect.com/106225/article
  • Peer Reviewed
• [Journal Article] Design of a 13C Magnetic Resonance Probe Using a DeuteratedMethoxy Group as a Long-Lived Hyperpolarization Unit. (2012)
  • Author(s): Doura T, Hata R, Nonaka H, Ichikawa K, Sando S
  • Journal Title: Angewandte Chemie Volume: 51(40) Pages: 10114-7
  • DOI: DOI:10.1002/anie.201202885
  • Peer Reviewed
• [Journal Article] Minocycline modulates human social decision-making: possible impact of microglia on personality-oriented social behaviors (2012)
  • Author(s): Kato TA, Watabe M, Tsuboi S, Ishikawa K, Hashiya K, Monji A, Utsumi H, Kanba S
  • Journal Title: PLoS One Volume: 7(7) Pages: e40461
  • DOI: DOI:10.1371/journal.pone.0040461
  • Peer Reviewed
• [Journal Article] These authors equally contributed to this work.]: Does minocycline, an antibiotic with inhibitory effects on microglial activation, sharpen a sense of trust in social interaction (2012)
  • Author(s): Watabe M*, Kato TA *, Monji A, Horikawa H, Kanba S
  • Journal Title: Psychopharmacology Volume: 220(3) Pages: 551-7
  • DOI: DOI:10.1007/s00213-011-2509-8
  • Peer Reviewed
• [Journal Article] In vivo toxicity and antitumor activity of mangosteen extract (2012)
  • Author(s): Kosem N, Ichikawa K, Utsumi H, Moongkarndi P
  • Journal Title: J Nat Med Volume: 67(2) Pages: 255-63
  • DOI: DOI:10.1016/j.freeradbiomed.2012.04.026
  • Peer Reviewed
• [Journal Article] Whole-body kinetic image of a redox probe in mice using Overhauser-enhanced MRI (2012)
  • Author(s): Kosem N, Naganuma T, Ichikawa K, Phumala Morales N, Yasukawa K, Hyodo F, Yamada K, Utsumi H
  • Journal Title: Free Radic Biol Med Volume: 53(2) Pages: 328-36
  • DOI: DOI:10.1016/j.freeradbiomed.2012.04.026
  • Peer Reviewed
• [Journal Article] Combination therapy of olmesartan and azelnidipine inhibits sympathetic activity associated with reducing oxidative stress in the brain of hypertensive rats. (2012)
  • Author(s): Shinohara K, Hirooka Y, Ogawa K, Kishi T, Yasukawa K, Utsumi H, Sunagawa K.
  • Journal Title: Clin Exp Hypertens Volume: 34(6) Pages: 456-62
  • DOI: doi: 10.3109/10641963.2012.666603.
  • Peer Reviewed
• [Journal Article] The detrimental effect of nitric oxide on tissue is associated with infl amatory events in the vascular endothelium and neutrophils in mice with dextran sodium sulfate-induced colitis (2012)
  • Author(s): Yasukawa K, Tokuda H, Tun X, Utsumi H, Yamada K.
  • Journal Title: Free Radic Res Volume: 46 Pages: 1427-36
  • DOI: doi:10.3109/10715762.2012.732698.
  • Peer Reviewed
• [Journal Article] Nitroxides prevent exacerbation of indomethacin-induced gastric damage in adjuvant arthritis rats. (2011)
  • Author(s): Deguchi H, Yasukawa K, Yamasaki T, Mito F, Kinoshita Y, Naganuma T, Sato S, Yamato M, Ichikawa K, Sakai K, Utsumi H, Yamada K.
  • Journal Title: Free Radic Biol Med Volume: 51(9) Pages: 1799-805
  • DOI: doi: 10.1016/j.freeradbiomed.2011.08.010.
  • Peer Reviewed
• [Journal Article] Overhauser-enhanced magnetic resonance imaging characterization of mitochondria functional changes in the 6-hydroxydopamine rat model. (2011)
  • Author(s): Yamato M, Shiba T, Naganuma T, Ichikawa K, Utsumi H, Yamada K.
  • Journal Title: Neurochem Int. Volume: 59(6) Pages: 804-11
  • DOI: doi: 10.1016/j.neuint.2011.08.010.
  • Peer Reviewed
• [Journal Article] In vivo imaging of mitochondrial function in methamphetamine-treated rats (2011)
  • Author(s): Shiba T, Yamato M, Kudo W, Watanabe T, Utsumi H, Yamada K.
  • Journal Title: Neuroimage Volume: 57(3) Pages: 866-72
  • DOI: doi: 10.1016/j.neuroimage.2011.05.041.
  • Peer Reviewed
• [Journal Article] Anti-Inflammatory properties of antipsychotics via microglia modulations: are antipsychotics a 'fire extinguisher' in the brain of schizophrenia? (2011)
  • Author(s): Kato TA, Monji A, Mizoguchi Y, Hashioka S, Horikawa H, Seki Y, Kasai M, Utsumi H, Kanba S.
  • Journal Title: Mini Rev Med Chem Volume: (7) Pages: 565-74
  • URL: http://www.eurekaselect.com/88180/article
  • Peer Reviewed
• [Journal Article] Aripiprazole inhibits superoxide generation from phorbol-myristate-acetate (PMA)-stimulated microglia in vitro: implication for antioxidative psychotropic actions via microglia (2011)
  • Author(s): Kato TA, Monji A, Yasukawa K, Mizoguchi Y, Horikawa H, Seki Y, Hashioka S, Han YH, Kasai M, Sonoda N, Hirata E, Maeda Y, Inoguchi T, Utsumi H, Kanba S
  • Journal Title: Schizophr Res. Volume: 129(2-3) Pages: 172-82
  • DOI: doi: 10.1016/j.schres.2011.03.019.
  • Peer Reviewed
• [Journal Article] Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension (2011)
  • Author(s): Hirooka Y, Kishi T, Sakai K, Takeshita A, Sunagawa K.,
  • Journal Title: Am J Physiol Regul Integr Comp Physiol. Volume: 300 Pages: R818-R826
  • DOI: doi: 10.1152/ajpregu.00426.2010.
  • Peer Reviewed
• [Journal Article] Are Japan's hikikomori and depression in young people spreading abroad? (2011)
  • Author(s): Kato TA, Shinfuku N, Sartorius N, Kanba S.
  • Journal Title: The Lancet Volume: 378 Pages: 1070
  • DOI: doi: 10.1016/S0140-6736(11)61475-X.
  • Peer Reviewed
• [Journal Article] Monitoring the aggregation processes of amyloid-β using a spin-labeled, fluorescent nitroxyl radical (2011)
  • Author(s): Mito F, Yamasaki T, Ito Y, Yamato M, Mino H, Sadasue H, Shirahama C, Sakai K, Utsumi H, Yamada K.
  • Journal Title: Chem Commun (Camb) Volume: 7:47(17) Pages: 5070-2
  • DOI: doi: 10.1039/c0cc05764a
  • Peer Reviewed
• [Journal Article] Structure-Reactivity Relationship of Piperidine Nitroxide: Electrochemical, ESR and Computational Studies (2011)
  • Author(s): Yamasaki T. Mito F. Ito Y. Pandian S. Kinoshita Y. Nakano K. Murugesan R. Sakai K. Utsumi H. Yamada K,
  • Journal Title: J Org Chem Volume: 76 Pages: 435-40
  • DOI: doi: 10.1021/jo101961m.
  • Peer Reviewed
• [Journal Article] Ultrahighly sensitive in situ metabolomic imaging for visualizing spatiotemporal metabolic behaviors. (2010)
  • Author(s): Miura D, Fujimura Y, Yamato M, Hyodo F, Utsumi H, Tachibana H, Wariishi H.
  • Journal Title: Anal Chem Volume: 82(23) Pages: 9789-96
  • DOI: doi: 10.1021/ac101998z.
  • Peer Reviewed
• [Journal Article] In vivo evaluation of nobel nitroxyl radicals with reduction stability (2010)
  • Author(s): Kinoshita Y, Yamada K, Yamasaki T, Mito F, Yamato M, Kosem N, Deguchi H, Shirahama C, Ito Y, Kitagawa K, Okukado N, Sakai K, Utsumi H.
  • Journal Title: Free Radic Biol Med Volume: 49(11) Pages: 1703-9
  • DOI: doi: 10.1016/j.freeradbiomed.2010.08.027.
  • Peer Reviewed
• [Journal Article] Dynamic nuclear polarization studies of redox-sensitive nitroxyl spin probes in liposomal solution (2010)
  • Author(s): Benial AM, Utsumi H, Ichikawa K, Murugesan R, Yamada K, Kinoshita Y, Naganuma T, Kato M.
  • Journal Title: J Magn Reson. Volume: 204(1) Pages: 131-8
  • DOI: doi: 10.1016/j.jmr.2010.02.016
  • Peer Reviewed
• [Journal Article] Impact of biopsychosocial factors on psychiatric training in Japan and overseas: Are psychiatrists oriented to mind, brain, or sociocultural issues? (2010)
  • Author(s): Kato TA, Tateno M, Nakano W, Balhara YP, Teo AR, Fujisawa D, Sasaki R, Ishida T, Kanba S.
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 64(5) Pages: 520-30
  • DOI: doi: 10.1111/j.1440-1819.2010.02133.x.
  • Peer Reviewed
• [Journal Article] Development of two-hour suicide intervention program among medical residents: First pilot trial. (2010)
  • Author(s): Kato TA, Suzuki Y, Sato R, Fujisawa D, Uehara K, Hashimoto N, Sawayama Y, Hayashi J, Kanba S, Otsuka K.
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 64(5) Pages: 531-40
  • DOI: doi: 10.1111/j.1440-1819.2010.02114.x.
  • Peer Reviewed
• [Journal Article] Inhibitory effects of SSRIs on IFN-γ induced microglial activation through the regulation of intracelluar calcium. (2010)
  • Author(s): Horikawa H, Kato TA, Mizoguchi Y, Monji A, Seki Y, Ohkuri T, Gotoh L, Yonaha M, Ueda T, Hashioka S, Kanba S.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 34 Pages: 1306-16
  • DOI: doi: 10.1016/j.pnpbp.2010.07.015.
  • Peer Reviewed
• [Journal Article] Determination of reactive oxygen species associated with the degeneration of dopaminergic neurons during dopamine metabolism. (2010)
  • Author(s): Yamato M, Kudo W, Shiba T, Yamada K, Watanabe T, Utsumi H
  • Journal Title: Free Radic Res. Volume: 44(3) Pages: 249?57
  • DOI: doi: 10.1016/j.pnpbp.2010.07.015.
  • Peer Reviewed
• [Journal Article] An EPR method for estimating activity of antioxidants in mouse skin using an anthralin-derived radical model (2010)
  • Author(s): Kawai S, Matsumoto K, Utsumi H.
  • Journal Title: Free Radic Res. Volume: 44(3) Pages: 267?74
  • DOI: doi: 10.3109/10715760903456100.
  • Peer Reviewed
• [Journal Article] Oxidative stress in the rostral ventrolateral medulla modulates excitatory and inhibitory inputs in spontaneously hypertensive rats.
  • Author(s): Nishihara M, Hirooka Y, Matsukawa R, Kishi T, Sunagawa K.
  • Journal Title: J Hypertens Volume: 30(1) Pages: 97-106
  • DOI: doi: 10.1097/HJH.0b013e32834e1df4
  • Peer Reviewed
• [Presentation] Development of Overhauser enhanced MRI for imaging in vivo Physiological function (2012)
  • Author(s): Ichikawa K
  • Organizer: The 10th International Symposium for Future Drug Discovery & Medical care. Hokkaido University
  • Place of Presentation: Sapporo (Invited Lecture)
  • Year and Date: 20121002-03
• [Presentation] 磁気共鳴イメージング法を用いたレドックス疾患の抗酸化物質の評価 (2012)
  • Author(s): 兵藤文紀
  • Organizer: 第51回電子スピンサイエンス学会年会
  • Place of Presentation: 札幌市
  • Year and Date: 2012-11-03
• [Presentation] Minocycline and aripiprazole inhibit oligodendrocyte damage from interferon-r-stimulated microglia in a co-culture model (2012)
  • Author(s): Kato TA, Seki Y, Monji A, Mizoguchi Y, Horikawa H, Sato-Kasai M, Hayakawa H, Yamauchi Y, Yoshiga D, Kanba S
  • Organizer: The 42th Society for Neuroscience Annual Meeting
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2012-10-16
• [Presentation] Imaging in vivo oxidative diseases using OMRI (2012)
  • Author(s): Ichikawa K
  • Organizer: Asia-Pasific EPR/ESR Symposium
  • Place of Presentation: Beijing, China
  • Year and Date: 2012-10-13
• [Presentation] Challenge for biomedical innovation by Redox Navigation at Kyushu University (2012)
  • Author(s): Utsumi H
  • Organizer: The 10th International Symposium for Future Drug Discovery & Medical care
  • Place of Presentation: Sapporo (Invited Lecture)
  • Year and Date: 2012-10-03
• [Presentation] Imaging in vivo oxidative diseases using OMRI (2012)
  • Author(s): Ichikawa K
  • Organizer: Conference of Zavoisky Award in Electron Paramagnetic Resonance Spectroscopy
  • Place of Presentation: Kazan,Russia. (Invited Lecture
  • Year and Date: 2012-09-26
• [Presentation] 磁気共鳴法による生理機能イメージング法の開発 (2012)
  • Author(s): 市川和洋
  • Organizer: 蛋白研セミナー「磁気共鳴の先端計測技術と生体系への展開」
  • Place of Presentation: 大阪大学蛋白質研究所、吹田市
  • Year and Date: 2012-07-31
• [Presentation] Redox Molecular Imaging of Mouse Inflammation Model (2012)
  • Author(s): Ichikawa K
  • Organizer: The 2nd International Symposium on Electron Spin Science
  • Place of Presentation: Matsushima
  • Year and Date: 2012-07-23
• [Presentation] Overhauser-MRI を用いた生体レドックス・薬物動態のイメージング (2012)
  • Author(s): 内海英雄
  • Organizer: よこはま NMR 構造生物学研究会第45回ワークショップ「イメージングと創薬」
  • Place of Presentation: 横浜市
  • Year and Date: 2012-07-11
• [Presentation] 酸化ストレス疾患解明のための生体レドックスイメージング法の開発 (2012)
  • Author(s): 兵藤文紀
  • Organizer: 第51回 日本生体医工学大会
  • Place of Presentation: 福岡市
  • Year and Date: 2012-05-11
• [Presentation] 生体レドックスの分子イメージングと病態解析 (2012)
  • Author(s): 内海英雄
  • Organizer: 日本薬学会第132 年会
  • Place of Presentation: 札幌市
  • Year and Date: 2012-03-30
• [Presentation] Novel Imaging OMRI for in vivo Redox (2012)
  • Author(s): Utsumi H
  • Organizer: Oxidative stress in congenital and acquired hemolytic anemia
  • Place of Presentation: Thailand. (Invited Lecture)
  • Year and Date: 2012-03-23
• [Presentation] 磁気共鳴法を用いた生体機能可視化法の開発 (2012)
  • Author(s): 兵藤文紀
  • Organizer: 第10回稲盛フロンティア研究講演会
  • Place of Presentation: 福岡市(招待講演)
  • Year and Date: 2012-01-17
• [Presentation] High field OMRI scanner for imaging in vivo functional information (2011)
  • Author(s): Ichikawa K
  • Organizer: 5th SFRR-Asia / 8th ASMRM / 11th J-mit
  • Place of Presentation: Kagoshima
  • Year and Date: 2011-09-01
• [Presentation] Molecular Imaging of Oxidative Stress using Nitroxyl Radical Compounds (2011)
  • Author(s): Hyodo F
  • Organizer: 日独国交150周年シンポ ジウム
  • Place of Presentation: Germany
  • Year and Date: 2011-06-30
• [Presentation] Seminar ofdepartment of pharmacy (2011)
  • Author(s): Hyodo F
  • Organizer: マーチンルーサー大学薬学部特別シンポジウム
  • Place of Presentation: Germany
  • Year and Date: 2011-06-29
• [Presentation] Nitroxyl probes to monitor in vivo redox status in disease state by OMRI (2010)
  • Author(s): Yasukawa K
  • Organizer: EPR 2010 13th JSPS Core-to-Core Symposium
  • Place of Presentation: San Juan, Puerto Rico, USA
  • Year and Date: 20100502-06
• [Presentation] Cytokines.Free Radicals and Schizophrenia-Microglia Hypothesis of Schizophrenia- (2010)
  • Author(s): Kato TA, Monji A, Kanba S
  • Organizer: World Psychiatric Association (WPA) International Congress 2010
  • Place of Presentation: Beijing, China
  • Year and Date: 2010-09-04
• [Presentation] Antioxidative effect of aripiprazole, a novel unique antipsychotic, via inhibiting superoxide generation from PMA-stimulated microglia (2010)
  • Author(s): Kato T, Monji A, Yasukawa K, Mizoguchi Y, Horikawa H, Seki Y, Yonaha M, Hashioka S, Han YH, Utsumi H, Kanba S
  • Organizer: CINP 2010
  • Place of Presentation: Hong Kong
  • Year and Date: 2010-06-07
• [Book] Methods Mol Biol, Brain redox imaging (2011)
  • Author(s): Matsumoto K, Hyodo F, Anzai K,Utsumi H, Mitchell J.B., Krishna M.C.
  • Total Pages: 397-419
• [Patent(Industrial Property Rights)] 磁場印加装置 (2012)
  • Inventor(s): 内海英雄、市川和洋、兵藤文紀、長沼辰弥、梶原秀則、飯倉淳、他 2 名
  • Industrial Property Rights Holder: 九州大学、日本レドックス、富士電機、日立金属
  • Industrial Property Number: 2012-148866
  • Filing Date: 2012-07-02
• [Patent(Industrial Property Rights)] 生体内因性分子の検出方法 (2012)
  • Inventor(s): 内海英雄、市川和洋、兵藤文紀
  • Industrial Property Rights Holder: 九州大学
  • Industrial Property Number: 5150822
  • Acquisition Date: 2012-12-14
• [Patent(Industrial Property Rights)] 生体内因性分子の検出方法 (2010)
  • Inventor(s): 内海英雄、兵藤文紀、市川和洋
  • Industrial Property Rights Holder: 九州大学
  • Industrial Property Number: PCT/JP2010/069386
  • Filing Date: 2010-10-29
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