脳神経活動解析のための新規光計測技術の開発

• Project/Area Number: 20656064
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: System engineering
• Research Institution: Waseda University
• Principal Investigator: 尾崎 美和子 早稲田大学, 総合研究機構, 教授 (30291058)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2010: ¥400,000 (Direct Cost: ¥400,000); Fiscal Year 2009: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 2008: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: ニューレグリン / 電極の形状 / 電極間比較 / プローブの開発 / アダプター / 温度感受性色素 / 分極誘導 / デバイス / 膜電位感受性色素

Research Abstract

これまでの我々の研究から、統合失調症関連遺伝子ニューレグリン(NRG)は50Hz付近から100Hz間の周波数刺激により膜貫通ドメインのすぐN末側で蛋白切断を受け細胞外に切り出されることが解っている。実際に、統合失調症患者の血液サンプルを用い、分泌型NRGの血中量と遺伝子多型を解析することにより、統合失調症患者では、その発病と改善に分泌型NRGの量が関与していることを明らかにした。また統合失調症患者の分泌型NRG量の変動が発病と関連があること、発病の際、前頭前野や聴覚野における50～80Hz付近の神経活動消失や乱れが観察されることから光計測系で分泌量と神経活動を同時計測し、その結果を脳刺激にフィードバックする仕組みを構築しようとしてきた。
そのため必要な蛍光物質を様々な角度から合成、スクリーニングを行った結果、脳機能(神経活動)を高感度で検出できる温度感受性色素を得ることができた。神経活動変化に伴う細胞内カルシウム濃度変化が発熱・吸熱反応を引き起こし、その変化を蛍光強度変化計測することにより検出するシステムである。一方、NRGの蛋白分断と分泌を追跡するための新規プローブの合成にも成功し、両者を同時観測可能なところまできた。また、脳深部の計測を可能にするため、バンドル化した光ファイバー表面に色素を塗布することにより脳深部に於ける光計測をミリセカンドの時間分解能、20～50マイクロメータの空間分解能で計測できるシステムとし、同時に光刺激も可能となった。実際に脳スライス、動物個体に応用することによりそのプロトタイプの評価を行っている。

Research Products

• [Journal Article] Transgenic mice overexpressing typel-neruegulinlβ display hyper locomotor activity reduced context dependent fear-learning and social interaction : implication for schizophrenia (2011)
  • Author(s): T Kato, Y Abe, H Sotoyama, A Kakita, R Kominami, S Hirokawa, M Ozaki, H Takahashi, H Nawa
  • Journal Title: Molecular Psychiatry Volume: 16(3) Pages: 307-320
  • Peer Reviewed
• [Journal Article] Fluorescent Imaging Technique Suppressing Background Signals by using Quencher-conjugated Peptide (2011)
  • Author(s): Satoshi Arai, Yoon Su-In, Atsushi Murata, Shinji Takeoka, Yixin Lu, Xiaoyu Wu, Miwako Ozaki
  • Journal Title: Biochem.Biophys.Res.Commun Volume: 404 Pages: 211-216
  • Peer Reviewed
• [Journal Article] Phenotypic Characterization of Transgenic Mice Overexpressing Neuregulin-1 (2010)
  • Author(s): T.Kato, Y Abe, M.Mizuno, K, Araki, N, Takei, F.Liang, M.Ozaki, H.Nawa
  • Journal Title: PLoS ONE Volume: 5(12)e14185 Pages: 1-12
  • Peer Reviewed
• [Journal Article] Construction of a "Turn-on" Fluorescent Probe System for His-tagged Proteins (2010)
  • Author(s): Atsushi Murata, Satoshi Arai, Yoon Su-In, Masao Takabayashi, Miwako Ozaki, Shinji Takeoka
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 20(23) Pages: 6905-6908
  • Peer Reviewed
• [Journal Article] Repeated administration of methamphetamine blocked cholecystokinin-octapeptide injection-induced c-fos mRNA expression without change in capsaicin-induced junD mRNA expression in rat cerebellum (2010)
  • Author(s): Mitsuko Hamamura, Miwako Ozaki, Yasuyuki Fukumaki
  • Journal Title: J.Neural Transmission Volume: 117 Pages: 1041-1053
  • Peer Reviewed
• [Journal Article] Measurement and comparison of serum neuregulin-1 immunoreactivity in control subjects and patients with schizophrenia ; An influence of its genetic polymorphism (2010)
  • Author(s): Masako Shibuya, Emiko Komi, Ran Wang, Taisuke Kato, Yuichiro Watanabe, Miwako Sakai, Miwako Ozaki, Toshiyuki Someya, Hiroyuki Nawa
  • Journal Title: J.Neural Transmission Volume: 117 Pages: 887-895
  • Peer Reviewed
• [Journal Article] In silico analysis of neuregulin-1 evolution in vertebrates (2010)
  • Author(s): Chihfong Chou, Miwako Ozaki
  • Journal Title: Biosci.Rep Volume: 30(4) Pages: 267-275
  • Peer Reviewed
• [Journal Article] Transgenic mice overexpressing typel-neruegulinl β display hyper locomotor activity reduced context dependent fear-learningand social interaction : implication for schizophrenia (2010)
  • Author(s): T Kato, Y Abe, H Sotoyama, A Kakita, R Kominami, S Hirokawa, M Ozaki, H Takahashi, H Nawa
  • Journal Title: Molecular Psychiatry (In press)
  • Peer Reviewed
• [Journal Article] In silico analysis of neuregulin-1 evolution in vertebrates (2010)
  • Author(s): Chih-Fong Chou, Miwako Ozaki
  • Journal Title: Biosci.Rep 30 Pages: 267-275
  • Peer Reviewed
• [Journal Article] 生命医療工学分野の最前線が抱える問題点-脳科学分野に於ける規制と規制緩和の必要性 (2010)
  • Author(s): 尾崎美和子
  • Journal Title: 原子力学会誌学術誌 10 Pages: 97-98
  • NAID: 10025874218
• [Journal Article] Schizophrenia and Neuregulin-1 (2009)
  • Author(s): Hiroyuki Nawa, Miwako Ozaki
  • Journal Title: Schizophrenia Frontier 10 Pages: 58-65
• [Journal Article] Schizophrenia and Neuregulin-1 (2009)
  • Author(s): Hiroyuki Nawa, Miwako Ozaki
  • Journal Title: Schizophrenia Frontier (In press)
• [Journal Article] Imaging of Molecular Dynamics Regulated by Electrical Activities in Neural Circuits and in Synapses (2008)
  • Author(s): Fujii R., Ichikawa M., Ozaki M.
  • Journal Title: Neurosignals 16 Pages: 260-277
  • Peer Reviewed
• [Journal Article] Neuregulin Receptors, ErbB are Localized in Micro domain Lipid Raft of Cerebellar Granule Cells with Different Neural Activities (2008)
  • Author(s): Takashi Amanuma, Soh Osuka, Eriko Osima, Ryo Taguchi, Yoshio Hiirabayashi, MiwakoOzaki
  • Journal Title: J. Jap Soc. Women Sci. 9 Pages: 51-58
  • NAID: 130001238288
  • Peer Reviewed
• [Journal Article] NRG-1 plays key roles in the formation and maintenance of the normal structure of cerebellum and neural network of the pontocerebellar mossy fiver system. Annual Meeting of Society for Neurochemistry, Workshop for young neuroscientists (2008)
  • Author(s): Tang Y, Fiengy L, Ozaki M
  • Journal Title: International Symposium on“Molecular Aspects of Brain aging and Neurological Disorders"and Annual Meeting of Society for Neurochemistry, Proceeding Pages: 24-25
  • Peer Reviewed
• [Presentation] 精神疾患診断と治療に向けての医療機器開発 (2011)
  • Author(s): 尾崎美和子
  • Organizer: 奈良女子大学の理学部化学科・機能化学講座セミナー
  • Place of Presentation: 奈良
  • Year and Date: 2011-01-25
• [Presentation] 精神疾患診断と治療に向けての医療機器開発～シンガポールとの連携～ (2010)
  • Author(s): Miwako Ozaki
  • Organizer: 神戸産学交流ワークショップ
  • Place of Presentation: 神戸
  • Year and Date: 2010-11-05
• [Presentation] Novel approaches for diagnosis and therapy of brain dysfunctions by using visualization- techniques (2010)
  • Author(s): Miwako Ozaki
  • Organizer: Singapore General Hospital Invited Seminar
  • Place of Presentation: Singapore
  • Year and Date: 2010-10-29
• [Presentation] Proteolytic Cleavage Mechanism of NRG1 through Protein Kinase C Signaling Pathway (2010)
  • Author(s): Su-In Yoon, Chih-Fong Chou, Miwako Ozaki
  • Organizer: DECADE OF THE MIND VI
  • Place of Presentation: Singapore
  • Year and Date: 2010-10-19
• [Presentation] New Diagnoses and Treatment for Schizophrenia (2010)
  • Author(s): Miwako Ozaki
  • Organizer: 1^<st> Anniversary Symposium of WABIOS
  • Place of Presentation: Singapore
  • Year and Date: 2010-09-05
• [Presentation] In silico analysis of neuregulin 1 evolution in vertebrates (2010)
  • Author(s): Chih-Fong Chou, Miwako Ozaki
  • Organizer: 1^<st> Anniversary Symposium of WABIOS
  • Place of Presentation: Singapore
  • Year and Date: 2010-09-05
• [Presentation] Proteolytic Cleavage Mechanism of NRG1 Through PKC Activity (2010)
  • Author(s): Su-In Yoon, Chih-Fong Chou, Miwako Ozaki
  • Organizer: 1^<st> Anniversary Symposium of WABIOS
  • Place of Presentation: Singapore
  • Year and Date: 2010-09-05
• [Presentation] Novel approaches for the study and therapy of brain dysfunctions by using visualization- technology of biological functions and neuro-devices (2010)
  • Author(s): Miwako Ozaki
  • Organizer: A : STAR 12R invited seminar
  • Place of Presentation: Singapore
  • Year and Date: 2010-07-27
• [Presentation] New techniques for application of brain diseases. (2010)
  • Author(s): Miwako Ozaki
  • Organizer: Closed meeting by Science and Engineering Research Council
  • Place of Presentation: Singapore
  • Year and Date: 2010-06-22
• [Presentation] Fluorescent "turn-on" system utilizing the quencher conjugated peptide toward specific protein labeling in live cells (2010)
  • Author(s): Yoon, S.I.Arai, S.Murata, A.Takabayashi, M.Wu, X.Lu, Y.Takeoka, S.Ozaki, M.
  • Organizer: BMB 2010 meeting (Biochemical molecular biology)
  • Place of Presentation: Kobe
• [Presentation] Optical Imaging Method : from Molecule to Mind (2010)
  • Author(s): Miwako Ozaki
  • Organizer: DECADE OF THE MIND VI
  • Place of Presentation: Singapore
• [Presentation] Fluorescent "turn-on" system utilizing the quencher-conjugated peptide toward specific protein labeling in live cells (2010)
  • Author(s): Yoon, S.I.Arai, S.Murata, A.Takabayashi, M.Wu, X.Lu, Y.Takeoka, S.Ozaki, M.
  • Organizer: Society for Neurochemistry (APSN)
  • Place of Presentation: Phuket
• [Presentation] Construction of off/on fluorescent probe targeting His-tagged protein (2010)
  • Author(s): Atsushi Murata, Satoshi Arai, Yoon Su-In, Masao Takabayashi, Miwako Ozaki, Shinji Takeoka
  • Organizer: World Molecular Imaging Congress
  • Place of Presentation: Kyoto
• [Presentation] Construction of off/on fluorescent probe targeting His-tagged protein (2010)
  • Author(s): Atsushi Murata, Satoshi Arai, Yoon Su-In, Masao Takabayashi, Miwako Ozaki, Shinji Takeoka
  • Organizer: American Chemical Society
  • Place of Presentation: San Francisco
• [Presentation] 脳科学分野の最前線-規制と規制緩和の必要 (2009)
  • Author(s): 尾崎美和子
  • Organizer: 化学技術戦略推進機構(JCII)講演会
  • Place of Presentation: 東京
  • Year and Date: 2009-12-15
• [Presentation] 脳高次機能と脳電気信号の役割 (2009)
  • Author(s): 尾崎美和子
  • Organizer: 国土交通省官僚OB会
  • Place of Presentation: 東京
  • Year and Date: 2009-11-06
• [Presentation] イノベーションと規制を考える (2009)
  • Author(s): 尾崎美和子
  • Organizer: ナイエンスアゴラ, 独立行政法人科学技術振興機構主催
  • Place of Presentation: 東京
  • Year and Date: 2009-11-03
• [Presentation] Deep Brain Stimulation(DBS)in movement disorders and mental disorders (2009)
  • Author(s): 尾崎美和子
  • Organizer: Division of Enforcement Conference, Medorotonic Inc
  • Place of Presentation: Minneapolis
  • Year and Date: 2009-10-20
• [Presentation] A molecular mechanism to regulate brain higher-order functions, -Fundamental principles for information processing- (2009)
  • Author(s): 尾崎美和子
  • Organizer: National University of Singapore and Waseda Bioscience Research Institute in Singapore(WABIOS)joint Symposium
  • Place of Presentation: Singapore
  • Year and Date: 2009-09-15
• [Presentation] Novel approaches for the study and therapy of brain dysfunctions using visualization technology for biological functions and intelligent Deep Brain Stimulation/Brain Machine Interface (2009)
  • Author(s): 尾崎美和子
  • Organizer: Waseda Bioscience Research Institute in Singapore(WABIOS)Opening Ceremony
  • Place of Presentation: Singapore
  • Year and Date: 2009-09-14
• [Presentation] Deep Brain Stimulation in movement disorders and mental disorders (2009)
  • Author(s): 尾崎美和子
  • Organizer: Beijing International Neurological Forum by the Military General Hospital of Beijing
  • Place of Presentation: Beijing
  • Year and Date: 2009-09-04
• [Presentation] In silico analysis of neuregulin-1 evolution in vertebrates (2009)
  • Author(s): Chihfong Chou, Miwako Ozaki
  • Organizer: The 32th Annual Meeting of Molecular Biology Society of Japan
  • Place of Presentation: Yokohama
• [Presentation] In silico analysis of neuregulin 1 evolution in vertebrates (2009)
  • Author(s): Chou CF, Ozaki M
  • Organizer: The 40^<th> Annual Meeting the Society for Neuroscience Society
  • Place of Presentation: Chicago
• [Presentation] In silico analysis of neuregulin 1 evolution in vertebrates (2009)
  • Author(s): Chou CF, Ozaki M
  • Organizer: The 32^<nd> Annual Meeting the Japan Neuroscience Society
  • Place of Presentation: Nagoya
• [Presentation] His-tag認識に伴う蛍光off/on機能を有するプローブの開発 (2009)
  • Author(s): 村田篤・新井敏・Su-In Yoon・尾崎美和子・武岡真司
  • Organizer: 第3回日本化学会関東支部大会
  • Place of Presentation: 東京
• [Presentation] Neureguin-1 dependent neural projections play critical roles in the formation of normal cerebellum and prefrontal cortex structure (2008)
  • Author(s): Miwako Ozaki
  • Organizer: International Symposium on“Molecular Aspects of Brain aging and Neurological Disorders "andAnnual Meeting of Society for Neurochemistry.
  • Place of Presentation: Amritsar, India
• [Presentation] NRG-1 plays key roles in the formation and maintenance of the normal structure of cerebellum andneural network of the pontocerebellar mossy fiver system. Annual Meeting of Society for Neurochemistry, Workshop for young neuroscientists (2008)
  • Author(s): Tang Y, Fiengy L, Ozaki M
  • Organizer: International Symposium on “Molecular Aspects of Brain aging and Neurological Disorders" and Annual Meeting of Society for Neurochemistry.
  • Place of Presentation: Amritsar, India
• [Presentation] 亜鉛イオンを介したHis-tag認識蛍光プローブの合成とその認識能 (2008)
  • Author(s): 村田篤, 新井敏, Su-In Yoon, 尾崎美和子, 武岡真司
  • Organizer: 日本ケミカルバイオロジー研究会第3回年会
  • Place of Presentation: 東京
• [Presentation] NRG-1 dependent neural projections play critical roles in the formation of normal cerebellum and prefrontal cortex structure (2008)
  • Author(s): Tang Y, Fengyi L, Ozaki M
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸市
• [Presentation] 亜鉛イオンを介したHis-tag認識蛍光プローブの合成とその認識能 (2008)
  • Author(s): 村田篤, 新井敏, Yoon Su-In, Wu Xiaoyu, Lu Yixin, 尾崎美和子, 武岡真司
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸市
• [Presentation] NRG-1 dependent neural projections play critical roles in the formation of normal cerebellum and prefrontal cortex structure (2008)
  • Author(s): Tang Y, Fengyi L, Ozaki M
  • Organizer: 第18回日本神経回路学会
  • Place of Presentation: つくば市
• [Book] Imaging of Neural Network - From Information Processing to Drug Design (2008)
  • Author(s): Miwako Ozaki
  • Total Pages: 327
  • Publisher: KARGER
• [Remarks]
  • URL: http://www.waseda.jp/WABIOS/japanese/index.html
• [Patent(Industrial Property Rights)] Selective Labeling Reagents for Target Biomacromolecule. (2010)
  • Inventor(s): 武岡真司・新井敏・村田篤・尾崎美和子・Yoon, Su-In
  • Industrial Property Rights Holder: 早稲田大学
  • Filing Date: 2010-08-13
  • Overseas
• [Patent(Industrial Property Rights)] 標的生体高分子の選択的標識剤 (2009)
  • Inventor(s): 武岡真司, 新井敏, 尾崎美和子
  • Industrial Property Rights Holder: 早稲田大学
  • Industrial Property Number: 2009-191497
  • Filing Date: 2009-08-20