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Chewing attenuates metastasis-promoting effects of chronic stress in mice in

Research Project

Project/Area Number 20K10065
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57050:Prosthodontics-related
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

Azuma Kagaku  産業医科大学, 医学部, 教授 (20273146)

Co-Investigator(Kenkyū-buntansha) 久保 金弥  名古屋女子大学, 健康科学部, 教授 (00329492)
飯沼 光生  朝日大学, 歯学部, 教授 (70184364)
小野塚 実  名古屋女子大学, 医療科学部, 教授 (90084780)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords転移がん / ストレス / 咀嚼刺激 / 慢性ストレス / 精神ストレス
Outline of Research at the Start

乳がんなど多くのがんの発症・進行及び転移のいずれも、ストレスによって促進されることが多数報告されている。我々は乳がんモデルラットにおいて、咀嚼による刺激(咀嚼刺激)が、ストレス軽減と乳腺腫瘍の体積を顕著に減少することを解明した。
そこで本研究では、転移がんモデルマウスを用い、ストレス負荷中に咀嚼刺激を行った場合と行わなかった場合において、転移がんの発症率、がん腫瘍の数と大きさの計測、及びストレスホルモンとその受容体発現、転移がん関連遺伝子と活性酸素による酸化ストレス、免疫担当細胞の浸潤、血管・リンパ管の新生を定量分析し、転移がん発症に及ぼす咀嚼刺激の影響を分子生物学的並びに免疫学的に解明する。

Outline of Final Research Achievements

We examined effects of chewing on lung metastasis of breast cancer in mouse exposing to chronic restraint stress. Human cancer cells were injected into the tail vein of female nude mice. Stress was induced by placing mice in a restraint tube for 7 weeks. Mice in the stress-with-chewing group were allowed to chew during experimental period. The number and size of lung metastatic nodules, blood corticosterone level and the expression of glucocorticoid receptor, adrenaline receptor were higher in stress mice, compared with control mice. As compared to stress group, the number and size of lung metastatic nodules, blood corticosterone level and the expression of glucocorticoid receptor, adrenaline receptor were lower in stress-with-chewing group. These findings showed that chewing could attenuated the promoting effects of chronic stress on lung metastasis by regulating stress hormones and their receptors, and the downstream signaling involving angiogenesis and oxidative stress.

Academic Significance and Societal Importance of the Research Achievements

ストレス緩和とストレス性転移がんの発症・進行に及ぼす咀嚼刺激の効果をシステム的に解明し、がん患者のヘルス・プロモーションを支える口腔器官の介入を世界初の情報として国内外に発信する上で、学術的かつ社会的に大きな意義がある。今後のがん患者の増加が医療費をさらに押し上げ、近い将来医療経済を揺るがすことが懸念されている中、がんの発症・転移素因が咀嚼刺激によって解除される機構が解明されることにより、「がん治療における口のケア」と同様に、「がん予防における咀嚼行為」の取り組みが可能になり、医療費の削減に大きく寄与することが期待できる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (30 results)

All 2023 2022 2021 2020 Other

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (18 results) Remarks (2 results)

  • [Journal Article] Maternal chewing alleviates prenatal stress-related neuroinflammation mediated by microglia in the hippocampus of the mouse offspring2023

    • Author(s)
      Hisada C, Kajimoto K, Tsugane H, Iinuma M, Azuma K, Kubo KY
    • Journal Title

      J Prosthodont Res

      Volume: on line Issue: 23 Pages: 5950-5950

    • DOI

      10.3390/cancers14235950

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deficiency of Wnt10a causes female infertility via the β-catenin/Cys19a1 pathway in mice2022

    • Author(s)
      Zhang J-H, Tasaki T, Tsukamoto M, Wang K-Y, Kubo KY, Azuma K
    • Journal Title

      Int J Med Sci

      Volume: 19 Issue: 4 Pages: 701-710

    • DOI

      10.7150/ijms.71127

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deletion of Wnt10a is implicated in hippocampal neurodegeneration in mice2022

    • Author(s)
      Zhang J-H, Tasaki T, Tsukamoto M, Wang K-Y, Kubo KY, Azuma K
    • Journal Title

      Biomedicines

      Volume: 10 Issue: 7 Pages: 1500-1500

    • DOI

      10.3390/biomedicines10071500

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oxidative stress causes muscle structural alterations via p38 MAPK signaling in COPD mouse model2022

    • Author(s)
      Mano Y, Tsukamoto M, Wang KY, Nabeshima T, Kosugi K, Tajima T, Yamanaka Y, Suzuki H, Kawasaki M, Nakamura E, Zhou Q, Azuma K, Nakashima T, Tamura Y, Kozaki K, Nakazato K, Li YS, Kawai K, Yatera K, Sakai A
    • Journal Title

      Journal of Bone and Mineral Metabolism

      Volume: 40 Issue: 6 Pages: 927-939

    • DOI

      10.1007/s00774-022-01371-1

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Environmental enrichment improves hypomyelination, synaptic alterations, and memory deficits caused by tooth loss in aged SAMP8 mice.2021

    • Author(s)
      Kin-ya Kubo, Akifumi Ogasawara, Hiroko Tsugane, Mitsuo Iinuma, Toru Takahashi, Kagaku Azuma
    • Journal Title

      Arch Oral Biol

      Volume: 123 Pages: 105039-105039

    • DOI

      10.1016/j.archoralbio.2021.105039

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chewing Behavior Attenuates the Tumor Progression‐Enhancing Effects of Psychological Stress in a Breast Cancer Model Mouse.2021

    • Author(s)
      Qian Zhou, Masahisa Katano, Jia‐He Zhang, Xiao Liu, Ke‐Yong Wang, Mitsuo Iinuma, Kin‐ya Kubo, Kagaku Azuma.
    • Journal Title

      Brain Sciences

      Volume: 11 Issue: 4 Pages: 479-479

    • DOI

      10.3390/brainsci11040479

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal chewing improves prenatal stress-induced cognitive deficit and anxiety-like behavior associated with alterations of the apoptotic response and serotonin pathway in mouse offspring.2021

    • Author(s)
      Kajimoto K, Hisada C, Ochi S, Yoshikawa E, Suzuki A, Tsugane H, Zhang J, Iinuma M, Kubo KY, Azuma K
    • Journal Title

      Arch Oral Biol

      Volume: 130 Pages: 105245-105245

    • DOI

      10.1016/j.archoralbio.2021.105245

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer's Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin2021

    • Author(s)
      Liu X, Zhou Q, Zhang JH, Wang KY, Saito T, Saido TC, Wang X, Gao X, Azuma K
    • Journal Title

      Cells

      Volume: 10 Issue: 11 Pages: 3261-3261

    • DOI

      10.3390/cells10113261

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tooth loss early in life induces hippocampal morphology remodeling in senescence-accelerated mouse prone 8 (SAMP8) mice2020

    • Author(s)
      Masahisa Katano, Kyoko Kajimoto, Mitsuo Iinuma, Kagaku Azuma, Kin-ya Kubo
    • Journal Title

      Int J Med Sci

      Volume: 17(4) Issue: 4 Pages: 517-524

    • DOI

      10.7150/ijms.40241

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of Maternal Chewing on Prenatal Stress-Induced Cognitive Impairments in the Offspring via Multiple Molecular Pathways2020

    • Author(s)
      Qian Zhou, Ayumi Suzuki, Mitsuo Iinuma, Ke-Yong Wang, Kin-ya Kubo, Kagaku Azuma.
    • Journal Title

      Int J Mol Sci

      Volume: 21 Issue: 16 Pages: 5627-5627

    • DOI

      10.3390/ijms21165627

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Wnt10Aはマウス海馬の形態と機能を維持するため必要である2022

    • Author(s)
      張 家赫、王 克鏞、林 春樹、安達泰弘、東 華岳
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Effects of masticatory movements during prenatal stress on hippocampal dendrites2022

    • Author(s)
      Ochi S, Yoshikawa E, Katano M, Suzuki A, Iinuma M, Azuma K, Kubo KY
    • Organizer
      第45回日本神経科学大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Maternal chewing during prenatal stress improves microglia-mediated neuroinflammation2022

    • Author(s)
      Kajimoto K, Hisada C, Ochi S, Tsugane H, Iinuma M, Azuma K, Kubo KY
    • Organizer
      第45回日本神経科学大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 母マウスの咀嚼運動が仔の海馬のミクログリアに及ぼす影響2022

    • Author(s)
      梶本京子、杉本勘太、久田智詠、越智鈴子、津金裕子、飯沼光生、斎藤一誠、東 華岳、久保金弥
    • Organizer
      第60回日本小児歯科学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 歯の早期喪失が海馬のBDNF発現と情動障害に及ぼす影響2022

    • Author(s)
      津金裕子、尾辻 渉、片野雅久、越智鈴子、梶本京子、鈴木あゆみ、斎藤一誠、飯沼光生、東 華岳、久保金弥
    • Organizer
      第60回日本小児歯科学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Wnt10A欠損マウスの海馬機能形態学的調査2021

    • Author(s)
      張 家赫、周 倩、劉 瀟、王 克鏞、林 春樹、安達泰弘、東 華岳
    • Organizer
      第126回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 妊娠母体の咀嚼運動が仔のLPS投与におけるミクログリアの活性化に及ぼす影響2021

    • Author(s)
      久田智詠、市橋豊雄、市橋幸子、津金裕子、林 櫻子、飯沼光生、斎藤一誠、東 華岳、久保金弥
    • Organizer
      第59回日本小児歯科学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Long-term tooth loss affects the hippocampal neuronal dendrite morphology in SAMP8 mice2021

    • Author(s)
      Yoshikawa E, Suzuki A, Iinuma M, Azuma K, Kubo KY
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Research-status Report
  • [Presentation] The potential role of early tooth loss in the pathogenesis of the App knock-in mouse model2021

    • Author(s)
      Ochi S, Saitoh T, Saido T, Iinuma M, Azuma K, Kubo KY
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Effects of maternal chewing during prenatal stress on microglia-mediated neuroinflammation in the hippocampus of the offspring2021

    • Author(s)
      Hisada C, Kajimoto K, Tsukane H, Iinuma M, Azuma K, Kubo KY
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 豊かな環境は老化促進モデルマウス(SAM)P8の歯の喪失によって誘発される髄鞘低形成、シナプス低形成および記憶障害を改善する2021

    • Author(s)
      久田智詠、吉川英里、梶本京子、津金裕子、飯沼光生、東 華岳、久保金弥
    • Organizer
      第36回老化促進モデルマウス(SAM)学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 乳がんの進行に対するストレスと咀嚼刺激の影響2021

    • Author(s)
      東 華岳、周 倩、張 家赫、久保金弥
    • Organizer
      第53回日本臨床分子形態学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 妊娠母体の咀嚼が仔マウス海馬の構造と機能に及ぼす影響2020

    • Author(s)
      Qian Zhou, 王 克鏞, 林 春樹, 安達泰弘, 久保金弥, 東  華岳
    • Organizer
      第125回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 歯の早期喪失が海馬の体積に及ぼす影響.2020

    • Author(s)
      吉川英里、松田成彦、岡野 哲、林 櫻子、飯沼光生、東 華岳、久保金弥
    • Organizer
      第58回日本小児歯科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 歯の早期喪失がアルツハイマー病の発症に及ぼす影響.2020

    • Author(s)
      越智鈴子、久田智詠、鈴木あゆみ、飯沼光生、東 華岳、久保金弥
    • Organizer
      第58回日本小児歯科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 若齢期における急性ストレス下での拒食行動は咀嚼運動で緩和される.2020

    • Author(s)
      林 櫻子、津金裕子、吉川英里、鈴木あゆみ、東 華岳、飯沼光生
    • Organizer
      第58回日本小児歯科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 歯の早期喪失が老化促進マウス(SAMP8)の海馬体積に影響する2020

    • Author(s)
      吉川英里、越智鈴子、久田智詠、片野雅久、梶本京子、林 櫻子、 鈴木あゆみ、津金裕子、飯沼光生、東 華岳、久保金弥
    • Organizer
      第35回老化促進モデルマウス(SAM)学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Long-term tooth loss affects the hippocampal volume and oligodendrocytes in SAMP8 mice.2020

    • Author(s)
      Eri Yoshikawa, Suzuko Ochi, Chie Hisada, Masahisa Katano, Kyoko Kajimoto, Sakurako Hayashi, Mitsuo Iinuma, Kagaku Azuma, Kin-ya Kubo
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Research-status Report
  • [Remarks] 咀嚼(そしゃく)と脳の研究所

    • URL

      http://www.imbs-mastication.org/

    • Related Report
      2021 Research-status Report
  • [Remarks] 産業医科大学医学部第1解剖学

    • URL

      https://www.uoeh-u.ac.jp/medicine/1kaibo.html

    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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