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Brain microenvironment that determines the direction of degeneration or regeneration of the olfactory bulb projection neurons coupled with the inflammatory status of the nasal cavity

Research Project

Project/Area Number 18K07395
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionKyorin University

Principal Investigator

Hasegawa-Ishii Sanae  杏林大学, 保健学部, 准教授 (40435863)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords鼻腔炎症 / 嗅球 / 精神疾患 / 脳と免疫 / 腸内細菌 / 脳 / ミクログリア / 免疫細胞 / うつ的行動 / 性差 / 嗅覚神経回路 / 嗅覚系神経回路 / 脳微小環境 / 嗅球萎縮 / ニューロンの変性と再生
Outline of Final Research Achievements

Chronic nasal inflammation can be a risk factor for psychiatric disorders. As the first step to reveal the mechanism, we compared the effects of nasal inflammation and odor deprivation on the olfactory bulb (OB). The results from the animal study using mouse model indicate that the OB was atrophied in both models; nasal inflammation induced the shrinkage of outer layers of the OB with neuroinflammation, while odor deprivation caused the shrinkage of inner layers with no neuroinflammation. The OB recovered from the atrophy when the nasal inflammation subsided, during which the odor input was needed. Next, gut microbiota of mice with nasal inflammation was analyzed by 16S rRNA analysis. Results indicate that microbiota of male, but not female, mice with chronic nasal inflammation was remarkably changed. Thus, nasal inflammation perturbed the homeostasis of the brain and gut microbiota, which might lead to the onset of psychiatric disorders. 953

Academic Significance and Societal Importance of the Research Achievements

嗅球の萎縮は、副鼻腔炎、アルツハイマー病、うつ病、不安障害などの患者で見られ、嗅覚障害の原因となり、患者の生活の質を低下する。本研究は、鼻腔炎症と嗅覚刺激遮断の嗅球における影響の違いを明らかにし、鼻腔炎症による嗅球の萎縮は、炎症が治まり嗅覚刺激が戻れば回復する可能性を示した。また、鼻腔炎症が脳及び腸内細菌叢を乱すことを明らかにし、精神神経疾患発症の原因となる可能性を示唆した。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (27 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (6 results) Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (12 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] Pennsylvania State University(米国)

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

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Michigan State University(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Pennsylvania State University(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Michigan State University(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Pennsylvania State University(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Increased cytokine expression in the choroid plexus stroma and epithelium in response to endotoxin-induced systemic inflammation in mice2021

    • Author(s)
      Shimada Atsuyoshi、Hasegawa-Ishii Sanae
    • Journal Title

      Toxicology Reports

      Volume: 8 Pages: 520-528

    • DOI

      10.1016/j.toxrep.2021.03.002

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sex-dependent differences in the gut microbiota following chronic nasal inflammation in adult mice2021

    • Author(s)
      Mishima Yuko、Osaki Takako、Shimada Atsuyoshi、Kamiya Shigeru、Hasegawa-Ishii Sanae
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 4640-4640

    • DOI

      10.1038/s41598-021-83896-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential Effects of Nasal Inflammation and Odor Deprivation on Layer-Specific Degeneration of the Mouse Olfactory Bulb2020

    • Author(s)
      Hasegawa-Ishii Sanae、Imamura Fumiaki、Nagayama Shin、Murata Makiko、Shimada Atsuyoshi
    • Journal Title

      eneuro

      Volume: 7 Issue: 2 Pages: 0403-19

    • DOI

      10.1523/eneuro.0403-19.2020

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mutation in Sodium-Glucose Cotransporter 2 Results in Down-Regulation of Amyloid Beta (A4) Precursor-Like Protein 1 in Young Age, Which May Lead to Poor Memory Retention in Old Age2020

    • Author(s)
      Unno Keiko、Takagi Yoshiichi、Konishi Tomokazu、Suzuki Mitsuhiro、Miyake Akiyuki、Kurotaki Takumi、Hase Tadashi、Meguro Shinichi、Shimada Atsuyoshi、Hasegawa-Ishii Sanae、Pervin Monira、Taguchi Kyoko、Nakamura Yoriyuki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 15 Pages: 5579-5579

    • DOI

      10.3390/ijms21155579

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Widespread time-dependent changes in tissue cytokine concentrations in brain regions during the acute phase of endotoxemia in mice2020

    • Author(s)
      Hasegawa-Ishii Sanae、Inaba Muneo、Shimada Atsuyoshi
    • Journal Title

      NeuroToxicology

      Volume: 76 Pages: 67-74

    • DOI

      10.1016/j.neuro.2019.10.006

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Theanine, the Main Amino Acid in Tea, Prevents Stress-Induced Brain Atrophy by Modifying Early Stress Responses2020

    • Author(s)
      Unno Keiko、Sumiyoshi Akira、Konishi Tomokazu、Hayashi Michiko、Taguchi Kyoko、Muguruma Yoshio、Inoue Koichi、Iguchi Kazuaki、Nonaka Hiroi、Kawashima Ryuta、Hasegawa-Ishii Sanae、Shimada Atsuyoshi、Nakamura Yoriyuki
    • Journal Title

      Nutrients

      Volume: 12 Issue: 1 Pages: 174-174

    • DOI

      10.3390/nu12010174

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Responses of perivascular macrophages to circulating lipopolysaccharides in the subfornical organ with special reference to endotoxin tolerance.2019

    • Author(s)
      Morita-Takemura S, Nakahara K, Hasegawa-Ishii S, Isonishi A, Tatsumi K, Okuda H, Tanaka T, Kitabatake M, Ito T, Wanaka A.
    • Journal Title

      J Neuroinflammation

      Volume: 16 Issue: 1 Pages: 39-51

    • DOI

      10.1186/s12974-019-1431-6

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuroplastic changes in the olfactory bulb associated with nasal inflammation in mice2019

    • Author(s)
      Hasegawa-Ishii Sanae、Shimada Atsuyoshi、Imamura Fumiaki
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: 143 Issue: 3 Pages: 978-989

    • DOI

      10.1016/j.jaci.2018.09.028

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Changes in the brain morphology and microenvironment caused by nasal inflammation.2020

    • Author(s)
      Hasegawa-Ishii S
    • Organizer
      10th Mind Body Interface Symposium
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 慢性鼻腔炎症マウスにおける腸内細菌叢の変動.2020

    • Author(s)
      三島 由祐子 大崎 敬子 神谷 茂 石井 さなえ
    • Organizer
      第53回日本無菌生物ノートバイオロジー学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] The differential effects of nasal inflammation and odor deprivation on the layer-specific degeneration of the olfactory bulb in mice.2019

    • Author(s)
      Hasegawa-Ishii S, Imamura F, and Shimada A
    • Organizer
      26th Annual Scientific Meeting of PsychoNeuroImmunology,
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Acute responses of intracranial macrophages to LPS-induced systemic inflammation in newborn mice.2019

    • Author(s)
      Shimada A, Miura A and Hasegawa-Ishii S
    • Organizer
      26th Annual Scientific Meeting of PsychoNeuroImmunology,
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Differential effects of nasal inflammation and odor deprivation on layer-specific degeneration of the olfactory bulb.2019

    • Author(s)
      Hasegawa-Ishii S, Imamura F, Shimada A.
    • Organizer
      42nd Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2019 Research-status Report
  • [Presentation] 慢性鼻腔炎症に誘導される脳組織の可塑的変化2019

    • Author(s)
      石井 さなえ, 島田 厚良
    • Organizer
      第48回杏林医学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Transcriptional Analysis of Astrocyte-driven Microglia Activation in the Inflammatory Response.2019

    • Author(s)
      Murata M, Hasegawa-Ishi S, Watabe K and Shimada A
    • Organizer
      42nd Annual Meeting of the Molecular Biology Society of Japan.
    • Related Report
      2019 Research-status Report
  • [Presentation] Nasal inflammatory stage-associated plastic changes in the olfactory bulb neurocircuit.2018

    • Author(s)
      Hasegawa-Ishii S, Shimada A, and Imamura F.
    • Organizer
      PNIRS 25th Annual Scientific Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Neuroplastic changes in the olfactory bulb after chronic nasal inflammation.2018

    • Author(s)
      Hasegawa-Ishii S
    • Organizer
      8th Annual Meeting of Mind-Body Interface International Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Plastic changes in the olfactory bulb coupled with the inflammatory status of the nasal cavity.2018

    • Author(s)
      Hasegawa-Ishii S, Shimada A, and Imamura F.
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Cytokine-mediated cell-cell interaction between choroid plexus epithelium and stroma in response to systemic inflammation2018

    • Author(s)
      Shimada A, Miura A and Hasegawa-Ishii S.
    • Organizer
      PNIRS 2018 25th Annual Scientific Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 全身炎症に応答する脈絡叢上皮と間質のサイトカインを介 した細胞間相互作用2018

    • Author(s)
      島田厚良, 三浦晶大, 石井さなえ
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Research-status Report
  • [Remarks] 教員紹介

    • URL

      https://www.kyorin-u.ac.jp/univ/faculty/health/education/staff/detail.php?id=hea40310

    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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