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齲蝕原性細菌感染に起因する脳出血・認知症の病態解明と革新的新規治療法の開発

Research Project

Project/Area Number 19J00106
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionOsaka University

Principal Investigator

齊藤 聡  大阪大学, 歯学研究科, 特別研究員(SPD) (40732996)

Project Period (FY) 2019-04-25 – 2022-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywordscnm / 微小出血 / 脳卒中 / 齲蝕 / 認知症
Outline of Research at the Start

脳出血は, 高血圧と関わりが深い1型脳小血管病と, アルツハイマー病・脳アミロイド血管症に起因する2型脳小血管病に共通する病態である. 齲蝕と脳卒中, 認知症との関係は以前から報告されてきたが, その機序についてはこれまで不明な点が多かった. 近年, 一部の齲蝕原性細菌のみが発現する, コラーゲン結合能を有するCnm蛋白の存在が明らかとなり, Cnm陽性S. mutans保菌者では, 脳微小出血が高頻度に認められることが明らかになった. そこで本研究では, このCnm陽性S. mutansと脳出血発症との関連について, 特にその病態メカニズムの解析を中心に検討する.

Outline of Annual Research Achievements

脳微小出血は、頭部MRI-T2star強調画像において小さな円形の低信号域として描出され、脳卒中や認知症と関連する。Streptococcus mutansは、う蝕の主要な原因菌であるが、コラーゲン結合タンパク質であるCnmを発現するcnm遺伝子をもつStreptococcus mutans (cnm陽性Streptococcus mutans) を口腔内に保有する症例においては、脳微小出血の有病率が有意に高いことが報告されている。本研究では、cnm陽性S.mutansと脳微小出血の発症との関係について、後方視的、縦断的に解析した。脳卒中症例3782名のうちcnm陽性S. mutansの保有の有無を調査した404名を同定し、その中からT2star強調画像を含む3tesla頭部MRIを180日以上の間隔を空けて2回以上施行されている症例を対象とした。cnm陽性S.mutansを保有する症例 (cnm陽性群) と保有しない症例 (cnm陰性群) で、Quasi-Poisson Regressionモデルを使用して、脳微小出血の新規発症率を比較した。対象となった111人中、21人がcnm陽性群であり、90人がcnm陰性群だった。血圧や抗血栓薬の内服の有無等の背景は2群間で概ね同等であったが、脳微小出血の新規発症率は、cnm陽性群で、特に深部領域で有意に高かった。年齢、性別、高血圧、腎機能障害を調整因子として、多変量解析を行っても、cnm陽性群の脳微小出血新規発症率は有意に高値であった。本研究から、cnm陽性S.mutansを口腔内に保有することが、特に深部領域での脳微小出血の発症と密接に関係していることが明らかになった。

Research Progress Status

翌年度、交付申請を辞退するため、記入しない。

Strategy for Future Research Activity

翌年度、交付申請を辞退するため、記入しない。

Report

(2 results)
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (22 results)

All 2020 2019 Other

All Int'l Joint Research (2 results) Journal Article (16 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 16 results,  Open Access: 13 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] University of Southampton(英国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Southampton(英国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Drug Repositioning for Alzheimer’s Disease: Finding Hidden Clues in Old Drugs2020

    • Author(s)
      Ihara Masafumi、Saito Satoshi
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 74 Issue: 4 Pages: 1013-1028

    • DOI

      10.3233/jad-200049

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Postprandial cerebral infarction resolved by extracranial-intracranial bypass surgery2020

    • Author(s)
      Ikenouchi Hajime、Yoshimoto Takeshi、Hamano Eika、Saito Satoshi、Fukuma Kazuki、Washida Kazuo、Hattori Yorito、Kataoka Hiroharu、Ihara Masafumi
    • Journal Title

      eNeurologicalSci

      Volume: 21 Pages: 100283-100283

    • DOI

      10.1016/j.ensci.2020.100283

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral carriage of Streptococcus mutans harboring the cnm gene is related to an increased incidence of cerebral microbleeds2020

    • Author(s)
      Hosoki S, Saito S, Tonomura S, Ishiyama H, Yoshimoto T, Ikeda S, Ikenouchi H, Yamamoto Y, Hattori Y, Miwa K, Friedland RP, Carare RO, Nakahara J, Suzuki N, Koga M, Toyoda K, Nomura R, Nakano K, Takegami M, Ihara M.
    • Journal Title

      Stroke

      Volume: 51 Issue: 12 Pages: 3632-3639

    • DOI

      10.1161/strokeaha.120.029607

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Various head rotations for ultrasonographic diagnosis of bilateral bow hunter’s syndrome2020

    • Author(s)
      Kimihira Luna、Yoshimoto Takeshi、Saito Satoshi、Hattori Yorito、Fukuma Kazuki、Washida Kazuo、Ihara Masafumi
    • Journal Title

      Acta Neurologica Belgica

      Volume: 120 Issue: 4 Pages: 1003-1005

    • DOI

      10.1007/s13760-020-01377-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Demonstrating a reduced capacity for removal of fluid from cerebral white matter and hypoxia in areas of white matter hyperintensity associated with age and dementia2020

    • Author(s)
      MacGregor Sharp Matthew、Saito Satoshi (Co-first author)、Keable Abby、Gatherer Maureen、Aldea Roxana、Agarwal Nivedita、Simpson Julie E.、Wharton Stephen B.、Weller Roy O.、Carare Roxana O.
    • Journal Title

      Acta Neuropathologica Communications

      Volume: 8 Issue: 1 Pages: 131-131

    • DOI

      10.1186/s40478-020-01009-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prevalence and Atypical Clinical Characteristics of NOTCH3 Mutations Among Patients Admitted for Acute Lacunar Infarctions2020

    • Author(s)
      Okada Takashi、Washida Kazuo、Irie Kenichi、Saito Satoshi、Noguchi Michio、Tomita Tsutomu、Koga Masatoshi、Toyoda Kazunori、Okazaki Shuhei、Koizumi Takashi、Mizuta Ikuko、Mizuno Toshiki、Ihara Masafumi
    • Journal Title

      Frontiers in Aging Neuroscience

      Volume: 12 Pages: 130-130

    • DOI

      10.3389/fnagi.2020.00130

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cerebral Amyloid Angiopathy Presenting as Massive Subarachnoid Haemorrhage: A Case Study and Review of Literature2020

    • Author(s)
      Saito Satoshi、Ikeda Yoshihiko、Ando Daisuke、Carare Roxana Octavia、Ishibashi-Ueda Hatsue、Ihara Masafumi
    • Journal Title

      Frontiers in Aging Neuroscience

      Volume: 12 Pages: 538456-538456

    • DOI

      10.3389/fnagi.2020.538456

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Editorial: Intramural Vascular Cells: Key Therapeutic Targets for Vascular Cognitive Impairment2020

    • Author(s)
      Saito Satoshi、McLaurin JoAnne、Carare Roxana Octavia
    • Journal Title

      Frontiers in Aging Neuroscience

      Volume: 12 Pages: 615780-615780

    • DOI

      10.3389/fnagi.2020.615780

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Potential Therapeutic Approaches for Cerebral Amyloid Angiopathy and Alzheimer’s Disease2020

    • Author(s)
      Tanaka Masashi、Saito Satoshi、Inoue Takayuki、Satoh-Asahara Noriko、Ihara Masafumi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 6 Pages: 1992-1992

    • DOI

      10.3390/ijms21061992

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy2020

    • Author(s)
      Owasil Raisah、O’Neill Ronan、Keable Abby、Nimmo Jacqui、MacGregor Sharp Matthew、Kelly Louise、Saito Satoshi、Simpson Julie E.、Weller Roy O.、Smith Colin、Attems Johannes、Wharton Stephen B.、Yuen Ho Ming、Carare Roxana O.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 4 Pages: 1225-1225

    • DOI

      10.3390/ijms21041225

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of fingolimod on oligodendrocyte maturation under prolonged cerebral hypoperfusion2019

    • Author(s)
      Yasuda Ken、Maki Takakuni、Saito Satoshi、Yamamoto Yumi、Kinoshita Hisanori、Choi Yoon Kyung、Arumugam Thiruma Valavan、Lim Yun-An、Chen Christopher Li Hsian、Wong Peter Tsun-Hon、Ihara Masafumi、Takahashi Ryosuke
    • Journal Title

      Brain Research

      Volume: 1720 Pages: 146294-146294

    • DOI

      10.1016/j.brainres.2019.06.013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Novel Therapeutic Potentials of Taxifolin for Amyloid-β-associated Neurodegenerative Diseases and Other Diseases: Recent Advances and Future Perspectives2019

    • Author(s)
      Tanaka Masashi、Saito Satoshi、Inoue Takayuki、Satoh-Asahara Noriko、Ihara Masafumi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 9 Pages: 2139-2139

    • DOI

      10.3390/ijms20092139

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of a Multicomponent Intervention to Prevent Alzheimer's Disease2019

    • Author(s)
      Saito Satoshi、Yamamoto Yumi、Ihara Masafumi
    • Journal Title

      Frontiers in Neurology

      Volume: 10 Pages: 490-490

    • DOI

      10.3389/fneur.2019.00490

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Dipeptidyl Peptidase-4 Inhibitor Linagliptin Ameliorates High-fat Induced Cognitive Decline in Tauopathy Model Mice2019

    • Author(s)
      Nakaoku Yuriko、Saito Satoshi、Yamamoto Yumi、Maki Takakuni、Takahashi Ryosuke、Ihara Masafumi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 10 Pages: 2539-2539

    • DOI

      10.3390/ijms20102539

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pleiotropic neuroprotective effects of taxifolin in cerebral amyloid angiopathy2019

    • Author(s)
      Inoue Takayuki、Saito Satoshi、Tanaka Masashi、Yamakage Hajime、Kusakabe Toru、Shimatsu Akira、Ihara Masafumi、Satoh-Asahara Noriko
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 116 Issue: 20 Pages: 10031-10038

    • DOI

      10.1073/pnas.1901659116

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Balloon-like Mobile Plaque in the Innominate Artery: Ultrasonographic and Pathological Perspectives of Repetitive Embolism2019

    • Author(s)
      Ikenouchi Hajime、Washida Kazuo、Yoshimoto Takeshi、Fukuma Kazuki、Saito Satoshi、Inoue Yosuke、Matsuda Hitoshi、Ihara Masafumi
    • Journal Title

      Journal of Stroke and Cerebrovascular Diseases

      Volume: 28 Issue: 7 Pages: e95-e97

    • DOI

      10.1016/j.jstrokecerebrovasdis.2019.04.015

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] Taxifolin is a novel therapeutic agent for Alzheimer’s disease and cerebral amyloid angiopathy.2020

    • Author(s)
      Saito Satoshi
    • Organizer
      AAIC
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アルツハイマー病と脳アミロイド血管症と白質病変2020

    • Author(s)
      齊藤聡
    • Organizer
      第39回日本認知症学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Taxifolin is a novel therapeutic agent for cerebral amyloid angiopathy.2020

    • Author(s)
      Saito, S., Tanaka, M., Satoh-Asahara, N., Carare, R. O., Weller, R. O., Ihara, M.
    • Organizer
      121st Meeting of the British Neuropathological Society.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 被験者の脳微小出血の重症化リスクを予測するための方法2020

    • Inventor(s)
      齊藤聡 他
    • Industrial Property Rights Holder
      齊藤聡 他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report

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Published: 2019-05-29   Modified: 2024-03-26  

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