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Are extracellular vesicles of periodontal pathogens that reach the brain involved in the onset and progression of Alzheimer's disease?

Research Project

Project/Area Number 20K23030
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0907:Oral science and related fields
Research InstitutionThe University of Tokushima

Principal Investigator

SEYAMA Mariko  徳島大学, 大学院医歯薬学研究部(歯学域), 助教 (30875787)

Project Period (FY) 2020-09-11 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords歯周病原菌 / アルツハイマー病 / 細胞外小胞 / 神経炎症 / ミクログリア / 行動試験
Outline of Research at the Start

歯周病原菌 Porphyromonas gingivalis (Pg) が放出した細胞外小胞(outer membrane vesicles, OMVs)が糖尿病を重症化させることを報告した。その過程で、菌固有の病原因子を豊富に含んだPg OMVs が、脳底部にも集積することを見出した。これは、Pg OMVs が脳内に侵入し、各種脳疾患の発症に関わっている可能性を示唆している。本研究では、歯周病とアルツハイマー病との関連性について、Pg OMVs の役割に着目して検証する。加えて、Pg OMVs に含有されるどの病原因子がアルツハイマー病の悪化に重要な影響を与えるかについて明らかにする。

Outline of Final Research Achievements

Periodontal diseases affect the pathology of Alzheimer’s diseases, whereas the molecular mechanisms have not been elucidated. In this study, we verified whether OMVs released from Porpyromonas gingivais (Pg OMVs) implicated in Alzheimer’s diseases. The injection of Pg OMVs for 12 weeks did not affect the cognitive function in the mice. In the brain of Pg OMVs-injected mice, the gingipains contained on Pg OMVs were detected, and microglias were activated. The pathological findings such as atrophy and demyelination were not observed. In human microglia HMC-3 cells, Pg OMVs decreased the gene expression of inflammatory cytokines. These results suggested that Pg OMVs which were produced in periodontal diseases may affects Altheimer’s diseases by delivering their virulence factor gingipains to the brain.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、歯周病がアルツハイマー病を悪化させる分子機序や科学的根拠の一端が提示された。この結果を社会に還元し、「アルツハイマー病の予防・治療における、口腔ケア(口腔健康管理)や歯周治療の重要性」を啓発して行きたい。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (2 results)

All 2021 2020

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] Extracellular vesicles of P. gingivalis-infected macrophages induce lung injury.2021

    • Author(s)
      Kayo Yoshida, Kaya Yoshida, Natsumi Fujiwara, Mariko Seyama, Kisho Ono, Hotaka Kawai, Jiajie Guo, Ziyi Wang, Yao Weng, Yaqiong Yu, Yoko Uchida-Fukuhara, Mika Ikegame, Akira Sasaki, Hitoshi Nagatsuka, Hiroshi Kamioka, Hirohiko Okamura, Kazumi Ozaki
    • Journal Title

      Biochim Biophys Acta - Molecular Basis of Disease

      Volume: 1867 Issue: 11 Pages: 166236-166236

    • DOI

      10.1016/j.bbadis.2021.166236

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 歯周病原菌感染マクロファージの細胞外小胞が肺炎を誘導する可能性の検証2020

    • Author(s)
      吉田 佳世, 吉田 賀弥, 瀬山 真莉子, 尾崎 和美
    • Organizer
      日本歯周病学会
    • Related Report
      2020 Research-status Report

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Published: 2020-09-29   Modified: 2023-01-30  

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