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Analysis of microbiota as a missing link between excercise and adult hippocampal neurogenesis

Research Project

Project/Area Number 19K22812
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research InstitutionKyushu University

Principal Investigator

Jinno Shozo  九州大学, 医学研究院, 教授 (10325524)

Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords腸内細菌叢 / 認知機能 / 成体海馬神経新生 / 短鎖脂肪酸 / 運動 / 加齢 / ミクログリア / Lactobacillus casei / 中間代謝産物 / 認知・情動
Outline of Research at the Start

近年、腸内細菌叢が脳機能に関わっていることが認識され、研究が急速に広まっている。興味深いことに、運動に伴って腸内細菌叢の変化が起こることも報告されている。我々は、豊かな環境による成体海馬神経新生の促進には、歯状回のコンドロイチン硫酸の増加が関わっていることを最近の報告で明らかにしたが、そのメカニズムは未解明のままである。これらを踏まえ我々は、マウスを用いた動物実験により、「運動は腸内細菌叢の中間代謝物を介して間接的に神経新生を促進する」との仮説に基づく分野横断的な検討に取り組む。本研究によって、運動による成体海馬神経新生の促進に腸内細菌叢が関与するメカニズムが明らかになると考えられる。

Outline of Final Research Achievements

We aimed to understand the potential role of microbiota and voluntary exercise in brain function. To this end, we analyzed young adult mice that exhibited higher locomotor activity and middle-aged mice that showed reduced locomotor activity. Interestingly, alterations in microbiota by probiotics (Lactobacillus casei) promoted the adult hippocampal neurogenesis and improved memory performance in middle-aged mice. By contrast, the administration of microbiota did not affect the results in young adult mice. The concentrations of short-chain fatty acid in feces were increased by probiotics, and administration of short-chain fatty acid promoted adult hippocampal neurogenesis in middle-aged mice. Pharmacological depletion of microglia by PLX3397 inhibited the effects of probiotics on memory performance and adult hippocampal neurogenesis. These findings suggest that microbiota may affect brain function via modulation of microglial activity in middle aged mice.

Academic Significance and Societal Importance of the Research Achievements

運動機能が低下する高齢者にみられるロコモティブシンドロームは、認知機能の低下や要介護に至るリスクを高めると考えられている。本研究で我々は、プロバイオティクスによる腸内細菌叢の改変は、運動量の多い若齢マウスの認知機能には影響を与えないが、運動量が減少している加齢マウスの認知機能を改善し、脳の免疫細胞であるミクログリアを介して成体海馬神経新生を促進することを発見した。本研究の意義は、加齢による筋力の低下や関節の痛みのため、適切な運動をすることが困難な高齢者にとり、腸内細菌叢の改善は認知機能低下を予防する可能性があることを明らかにした点にある。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (30 results)

All 2022 2021 2020 2019 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 1 results) Presentation (17 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Phytoestrogen genistein modulates neuron-microglia signaling in a mouse model of chronic social defeat stress2022

    • Author(s)
      Risako Fujikawa, Jun Yamada, Kyoko M Iinuma, Shozo Jinno
    • Journal Title

      Neuropharmacology

      Volume: 206 Pages: 108941-108941

    • DOI

      10.1016/j.neuropharm.2021.108941

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signal Transducer and Activator of Transcription 3 Activation in Hippocampal Neural Stem Cells and Cognitive Deficits in Mice Following Short-term Cuprizone Exposure2021

    • Author(s)
      Ohgomori Tomohiro、Jinno Shozo
    • Journal Title

      Neuroscience

      Volume: 472 Pages: 90-102

    • DOI

      10.1016/j.neuroscience.2021.07.031

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A unique subtype of ramified microglia associated with synapses in the rat hippocampus2021

    • Author(s)
      Ohgomori Tomohiro、Iinuma Kyoko、Yamada Jun、Jinno Shozo
    • Journal Title

      European Journal of Neuroscience

      Volume: 54 Issue: 3 Pages: 4740-4754

    • DOI

      10.1111/ejn.15330

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Subclass imbalance of parvalbumin-expressing GABAergic neurons in the hippocampus of a mouse ketamine model for schizophrenia, with reference to perineuronal nets2021

    • Author(s)
      Risako Fujikawa, Jun Yamada, Shozo Jinno
    • Journal Title

      Schizophre Res

      Volume: - Pages: 80-93

    • DOI

      10.1016/j.schres.2020.11.016

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Modulation of neuropathology and cognitive deficits by lipopolysaccharide preconditioning in a mouse pilocarpine model of status epilepticus2020

    • Author(s)
      Ohgomori Tomohiro、Jinno Shozo
    • Journal Title

      Neuropharmacology

      Volume: 176 Pages: 108227-108227

    • DOI

      10.1016/j.neuropharm.2020.108227

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] PSA-NCAM colocalized with cholecystokinin-expressing cells in the hippocampus is involved in mediating antidepressant efficacy2020

    • Author(s)
      Jun Yamada, Chihiro Sato, Kotarou Konno, Masahiko Watanabe, Shozo Jinno.
    • Journal Title

      The Journal of Neuroscience

      Volume: 40 Issue: 4 Pages: 825-842

    • DOI

      10.1523/jneurosci.1779-19.2019

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Promotion of synaptogenesis and neural circuit development by exosomes.2019

    • Author(s)
      Jun Yamada, Shozo Jinno
    • Journal Title

      Annals of Translationl Medicine

      Volume: 7 Issue: S8 Pages: S323-S323

    • DOI

      10.21037/atm.2019.09.154

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential link between antidepressant-like effects of ketamine and promotion of adult neurogenesis in the ventral hippocampus of mice.2019

    • Author(s)
      Jun Yamada, Shozo Jinno
    • Journal Title

      Neuropharmacology

      Volume: 158 Pages: 107710-107710

    • DOI

      10.1016/j.neuropharm.2019.107710

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] The expression of keratan sulfate reveals a unique subset of microglia in the mouse hippocampus after pilocarpine‐induced status epileptics2019

    • Author(s)
      Ohgomori Tomohiro、Jinno Shozo
    • Journal Title

      Journal of Comparative Neurology

      Volume: 528 Issue: 1 Pages: 18-35

    • DOI

      10.1002/cne.24734

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] メマンチンによるコンドロイチン硫酸量の増加を介した成体海馬神経新生の促進2022

    • Author(s)
      山田純, 神野尚三
    • Organizer
      第127回日本解剖学会総会・学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] マウス海馬のコンドロイチン硫酸の発現と神経新生に対するリポ多糖とセサミンの作用 に関する解析2022

    • Author(s)
      前田祥一朗, 山田純, 神野尚三
    • Organizer
      第127回日本解剖学会総会・学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] A novel treatment for cocaine dependence by ketamine via promotion of adult hippocampal neurogenesis2021

    • Author(s)
      Jun Yamada, Shoichiro Maeda, Kyoko Iinuma, Shozo Jinno
    • Organizer
      The 44th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2021 Annual Research Report
  • [Presentation] Morphological phenotypes of hippocampal microglia determining the vulnerability and resiliency to social defeat stress2021

    • Author(s)
      Risako Fujikawa, Shozo Jinno
    • Organizer
      The 44th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2021 Annual Research Report
  • [Presentation] Promotion of adult hippocampal neurogenesis by memantine via enhancement of chondroitin sulfate proteoglycan expression in middle-aged mice2021

    • Author(s)
      Jun Yamada, Shouichiro Maeda, Kyoko Iinuma, Shozo Jinno
    • Organizer
      第126回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Involvement of hippocampal microglia in vulnerability and resistance to social defeat stress2021

    • Author(s)
      Risako Fujikawa, Shozo Jinno
    • Organizer
      第126回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Enhanced quiescence of neural stem cells in the hippocampus by short-term exposure to cuprizone, a mouse model for schizophrenia2021

    • Author(s)
      Tomohiro Ohgomori, Shozo Jinno
    • Organizer
      第126回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Dysfunction hippocampal oligodendrocytes in the mouse model for posttraumatic stress disorder2021

    • Author(s)
      Shozo Jinno
    • Organizer
      第126回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Olig2-positive astrocyte in the hippocampus of a mouse model of temporal lobe epilepsy2020

    • Author(s)
      Tomohiro Ohgomori, Shozo Jinno
    • Organizer
      The 43rd Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2020 Research-status Report
  • [Presentation] Potential therapeutic effects of ketamine for cocaine addiction via promotion of adult hippocampal neurogenesis2020

    • Author(s)
      Jun Yamada, Shozo Jinno
    • Organizer
      The 43rd Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2020 Research-status Report
  • [Presentation] Neuroinflammation in the hippocampus of female mice exposed to social defeat stress2020

    • Author(s)
      Risako Fujikawa, Jun Yamada, and Shozo Jinno
    • Organizer
      The 43rd Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2020 Research-status Report
  • [Presentation] 社会的敗北ストレスに起因する海馬の神経炎症に対するゲニステインの効果2020

    • Author(s)
      藤川理沙子、山田純、神野尚三
    • Organizer
      第125回日本解剖学会総会・全国学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 新たな統合失調症モデルとしてのクプリゾン短期暴露マウスにおいて成体海馬神経新生が抑制されるメカニズム2020

    • Author(s)
      大篭友博、神野尚三
    • Organizer
      第125回日本解剖学会総会・全国学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 海馬のバーシカン陽性ペリニューロナルネットはneurogliaform cellの周囲に選択的に形成されている2020

    • Author(s)
      山田純、神野尚三
    • Organizer
      第125回日本解剖学会総会・全国学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Involvement of keratan sulfate-expressing hippocampal microglia in epileptogenesis via innate immune system2019

    • Author(s)
      Tomohiro Ohgomori, Shozo Jinno
    • Organizer
      The 42nd Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2019 Research-status Report
  • [Presentation] Subclass-dependent changes of parvalbumin-expressing neurons and perineuronal nets in the hippocampus of a mouse ketamine model for schizophrenia2019

    • Author(s)
      Risako Fujikawa, Jun Yamada, and Shozo Jinno
    • Organizer
      The 42nd Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2019 Research-status Report
  • [Presentation] Myelination of the axons derived from parvalbumin-expressing GABAergic neurons in the mouse hippocampus: time course, topography, and functional implications2019

    • Author(s)
      Jun Yamada, Shozo Jinno
    • Organizer
      The 42nd Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2019 Research-status Report
  • [Book] ひと目でわかる 脳のしくみとはたらき図鑑2022

    • Author(s)
      黒木 俊秀、神野 尚三、小野 良平
    • Total Pages
      224
    • Publisher
      創元社
    • ISBN
      9784422410999
    • Related Report
      2021 Annual Research Report
  • [Book] The Neuroscience of Aging 1st Edition2021

    • Author(s)
      Colin Martin, Victor Preedy, Rajkumar Rajendram
    • Total Pages
      1500
    • Publisher
      Elsevier
    • ISBN
      9780128183694
    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Remarks] 九州大学 大学院医学研究院 神経解剖学分野

    • URL

      https://anat.neurosci.kyushu-u.ac.jp/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 「やる気」の回復を促す脳内分子を発見~ポリシアル酸は海馬のセロトニンシグナル伝達を増強する~

    • URL

      https://www.kyushu-u.ac.jp/ja/researches/view/414

    • Related Report
      2019 Research-status Report

URL: 

Published: 2019-07-04   Modified: 2023-01-30  

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