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A study to elucidate mechanism, by which periodontists inducing memory impairment and to determine effect of its intervention on progression of dementia.

Research Project

Project/Area Number 16H05559
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Social dentistry
Research InstitutionNagoya City University

Principal Investigator

Michikawa Makoto  名古屋市立大学, 大学院医学研究科, 教授 (40270912)

Co-Investigator(Kenkyū-buntansha) 赤津 裕康  名古屋市立大学, 大学院医学研究科, 教授 (00399734)
橋詰 良夫  医療法人さわらび会福祉村病院長寿医学研究所, 神経病理研究所, 所長 (70106227)
佐藤 聡  日本歯科大学, 新潟生命歯学部, 教授 (70235357)
両角 祐子 (廣木祐子)  日本歯科大学, 新潟生命歯学部, 准教授 (90318551)
Research Collaborator Shirono Miwa  
Yoshioka Hiroo  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2016: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywords歯周病 / アルツハイマー病 / 口腔ケア / 認知症予防 / 歯牙欠損 / ソフトダイエット / 咀嚼機能低下 / 認知症 / 認知症進行抑止 / 介入試験
Outline of Final Research Achievements

We found that periodontitis caused memory impairment accompanied by increased levels of Ab deposition in Alzheimer’s disease mouse model. Brain inflammation demonstrated by increased levels of cytokines (IL-6, and TNFa) was found in mice with periodontitis. These results indicated that oral chronic inflammation caused by periodontitis invades into brain where cytokines levels increase and leading to increase Ab generation and Ab deposition, causing memory inflammation. We also found that intervention by treatment of periodontitis attenuated progression of memory deterioration in demented patients with Alzheimer’s disease.

Academic Significance and Societal Importance of the Research Achievements

歯周病の炎症が脳内に波及し、アルツハイマー病分子病態の増悪ならびに認知機能詳細を促進させることをマウスモデルで明らかにした。また、認知症および軽度認知症の患者に対して介入試験を行い、歯周病の治療、口腔ケアによる介入によって認知症の進行が抑制されることを示唆するデータを得た。これらの成果は、歯周病の治療、口腔ケアをすることにより認知症の予防ならびに認知機能の低下を抑止できる可能性を示しており、今後の大規模な研究の基盤となる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (24 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 10 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] スタンフォード大学(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Tau Depletion in APP Transgenic Mice Attenuates Task-Related Hyperactivation of the Hippocampus and Differentially Influences Locomotor Activity and Spatial Memory2018

    • Author(s)
      Yoshikawa Misato、Soeda Yoshiyuki、Michikawa Makoto、Almeida Osborne F. X.、Takashima Akihiko
    • Journal Title

      Frontiers in Neuroscience

      Volume: 12 Pages: 124-124

    • DOI

      10.3389/fnins.2018.00124

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nasal obstruction during adolescence induces memory/learning impairments associated with BDNF/TrkB signaling pathway hypofunction and high corticosterone levels2018

    • Author(s)
      Ogawa Takuya、Okihara Hidemasa、Kokai Satoshi、Abe Yasunori、Karin Harumi Uchima Koecklin、Makiguchi Mio、Kato Chiho、Yabushita Tadachika、Michikawa Makoto、Ono Takashi
    • Journal Title

      Journal of Neuroscience Research

      Volume: 96 Issue: 6 Pages: 1056-1065

    • DOI

      10.1002/jnr.24216

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Defensive effect of microRNA-200b/c against amyloid-beta peptide-induced toxicity in Alzheimer's disease models2018

    • Author(s)
      Higaki Sayuri、Muramatsu Masashi、Matsuda Akio、Matsumoto Kenji、Satoh Jun-ichi、Michikawa Makoto、Niida Shumpei
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 5 Pages: e0196929-e0196929

    • DOI

      10.1371/journal.pone.0196929

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deficiency of a sulfotransferase for sialic acid-modified glycans mitigates Alzheimer's pathology.2017

    • Author(s)
      Zhang Z, Takeda-Uchimura Y, Foyez T, Ohtake-Niimi S, Narentuya, Akatsu H, Nishitsuji K, Michikawa M, Wyss-Coray T, Kadomatsu K, Uchimura K.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 114(14) Issue: 14 Pages: 114-114

    • DOI

      10.1073/pnas.1615036114

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Periodontitis induced by bacterial infection exacerbates features of Alzheimer's disease in transgenic mice2017

    • Author(s)
      Ishida N, Ishihara Y, Ishida K, Tada H, Funaki-Kato Y, Hagiwara M, Ferdous T, Abdullah M, Mitani A, Michikawa M, Matsushita K.
    • Journal Title

      NPJ Aging Mech. Dis.

      Volume: 3 Issue: 1 Pages: 15-15

    • DOI

      10.1038/s41514-017-0015-x

    • NAID

      120006576159

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sodium balance, circadian BP rhythm, heart rate variability, and intrarenal renin-angiotensin-aldosterone and dopaminergic systems in acute phase of ARB therapy2017

    • Author(s)
      Isobe-Sasaki Yukako、Fukuda Michio、Ogiyama Yoshiaki、Sato Ryo、Miura Toshiyuki、Fuwa Daisuke、Mizuno Masashi、Matsuoka Tetsuhei、Shibata Hiroko、Ito Hiroyuki、Ono Minamo、Abe-Dohmae Sumiko、Kiyono Ken、Yamamoto Yoshiharu、Kobori Hiroyuki、Michikawa Makoto、Hayano Junichiro、Ohte Nobuyuki
    • Journal Title

      Physiological Reports

      Volume: 5 Issue: 11 Pages: e13309-e13309

    • DOI

      10.14814/phy2.13309

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phosphatidylcholine protects neurons from toxic effects of amyloid beta-protein in culture.2016

    • Author(s)
      Ko M, Hattori T, Abdullah M, Gong JS, Yamane T, Michikawa M.
    • Journal Title

      Brain Res

      Volume: 1642 Pages: 376-383

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ABCG1 and ABCG4 Suppress γ-Secretase Activity and Amyloid β Production2016

    • Author(s)
      Osamu Sano, Maki Tsujita, Yuuji Shimizu, Reiko Kato, Aya Kobayashi, Noriyuki Kioka, Alan T Remaley, Makoto Michikawa, Kazumitsu Ueda, and Michinori Matsuo
    • Journal Title

      PLoS One

      Volume: 11 Issue: 5 Pages: e0155400-e0155400

    • DOI

      10.1371/journal.pone.0155400

    • NAID

      120005997762

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Aβ reduces exosome release from astrocytes by enhancing JNK phosphorylation2016

    • Author(s)
      Abdullah M, Takase H, Nunome M, Enomoto H, Ito J-I, Gong J-S, and Michikawa M.
    • Journal Title

      J Alzhiemr Dis,

      Volume: 53 Issue: 4 Pages: 1433-1441

    • DOI

      10.3233/jad-160292

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tooth loss might not alter molecular pathogenesis in an aged transgenic Alzheimer's disease model mouse2015

    • Author(s)
      Oue H, Miyamoto Y, Koretake K, Okada S, Doi K, Jung CG, Michikawa M and Akagawa Y
    • Journal Title

      Gerodontology

      Volume: in press Issue: 3 Pages: 308-14

    • DOI

      10.1111/ger.12153

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] 認知症の危険因子・防御因子2018

    • Author(s)
      道川 誠
    • Organizer
      日本認知症学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Iron-treatment enhances γ-secretase activity and inhibits amyloid depostion2018

    • Author(s)
      鄒 鶤、沈 雪峰、藤田 融、菊地 光太、Arshad Noorani、Sadequl Islam、  駒野 宏人、道川 誠
    • Organizer
      日本認知症学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞内アダプター分子X11Lを介したApoE4による細胞内情報伝達機構の解明2018

    • Author(s)
      郭 家伶、豊田 めぐみ、中矢 正、道川 誠、鈴木 利治
    • Organizer
      日本認知症学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Regulation of expression and release of ApoE in cultured astrocytes2018

    • Author(s)
      アブドラ モハンマド、フェルドス タスリマ、キョウ建生、鄭 且均、道川 誠
    • Organizer
      日本認知症学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Effect of lactoferrin on ApoE secretion from cultured astrocytes2018

    • Author(s)
      Jung CG, Abdelhamid M, Abdullah M, Zhou CY, Wakabayashi H, Yamauchi K, Abe F, Michikawa M
    • Organizer
      日本認知症学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Analysis of phospholipid species in AD model mouse brain by LC-MS/MS2018

    • Author(s)
      Haque MD, Sheikh Abdullah、長子 晴美、堺 弘道、Azad  Abul, 土屋 美加子、道川 誠、長井 篤
    • Organizer
      日本認知症学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 歯の喪失がアルツハイマー病を誘発させるメカニズムについて2018

    • Author(s)
      後藤 哲哉、倉本 恵梨子、 ダール アシス、松本 信英、原 博満、山中 淳之、岩井 治樹、道川 誠
    • Organizer
      日本認知症学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 歯周病・咀嚼機能低下がアルツハイマー病分子病態ならびに認知機能に及ぼす影響2016

    • Author(s)
      道川誠
    • Organizer
      第6回日本認知症予防学会
    • Place of Presentation
      東北大学(宮城県、仙台市)
    • Year and Date
      2016-09-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] 認知症の正しい理解と歯科・口腔疾患との関連2016

    • Author(s)
      道川誠
    • Organizer
      第61回日本口腔外科学会
    • Place of Presentation
      幕張メッセ(千葉県、千葉市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Patent(Industrial Property Rights)] アポリポ蛋白E産生促進用組成物2018

    • Inventor(s)
      道川誠,湯田直樹、田中美順
    • Industrial Property Rights Holder
      道川誠,湯田直樹、田中美順
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-154553
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 認知機能改善用組成物2018

    • Inventor(s)
      道川誠、鄭 且均、若林裕之、中野学、武藤夏美
    • Industrial Property Rights Holder
      道川誠、鄭 且均、若林裕之、中野学、武藤夏美
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-190251
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 脳内の細胞外シグナル制御キナーゼリン酸化促進用組成物2018

    • Inventor(s)
      道川誠、鄭 且均、若林裕之、中野学、武藤夏美
    • Industrial Property Rights Holder
      道川誠、鄭 且均、若林裕之、中野学、武藤夏美
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-190255
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] アルツハイマー病バイオマーカー2018

    • Inventor(s)
      道川誠、赤津裕康、アブドラモハンマド、松原悦朗、木村成志
    • Industrial Property Rights Holder
      道川誠、赤津裕康、アブドラモハンマド、松原悦朗、木村成志
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas

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Published: 2016-04-21   Modified: 2022-01-28  

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