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Glutamate receptors-mediated sensory long-term facilitation of the carotid body in a rat model of sleep apnea syndrome

Research Project

Project/Area Number 22K06813
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48010:Anatomy-related
Research InstitutionIwate University (2023-2024)
Iwate Medical University (2022)

Principal Investigator

Yokoyama Takuya  岩手大学, 農学部, 准教授 (70772094)

Co-Investigator(Kenkyū-buntansha) 齋野 朝幸  岩手医科大学, 医学部, 教授 (40305991)
東尾 浩典  岩手医科大学, 教養教育センター, 准教授 (50342837)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2024: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords頸動脈小体 / グルタミン酸受容体 / 睡眠時無呼吸症候群 / グルタミン酸 / セロトニン / ADP
Outline of Research at the Start

慢性間欠的低酸素曝露により睡眠時無呼吸症候群(SAS)のモデル動物を作製し、頸動脈小体に生じるグルタミン酸受容体の発現増強を捉える。イメージング解析により、NMDA受容体の活性化とAMPA受容体数の増加に起因する化学受容細胞の興奮増強を明らかにする。グルタミン酸受容体依存的に頸動脈洞枝の感覚性長期増強が生じることを立証する。これらの解析から、SASモデル動物の頸動脈小体におけるグルタミン酸受容体による長期増強発現機構を解明する。

Outline of Final Research Achievements

In a rat model of sleep apnea syndrome (SAS) created by chronic intermittent hypoxic exposure, it has been reported that the sensory long-term facilitation, a sustained increase in nerve activity, is induced in the carotid sinus nerve that transmits carotid body excitation to the central nervous system. Inspired by the involvement of glutamate receptors in long-term potentiation in the central nervous system, the present study examined the expression of AMPA receptors in the carotid body of rats raised in room air. RT-PCR showed mRNA expression of GluA1 and GluA2 in the carotid body. Immunohistochemistry showed GluA1 immunoreactivity in some chemoreceptor cells. These results suggest that AMPA receptor-mediated glutamatergic pathway in the carotid body. However, no changes were observed in the expression of AMPA- and NMDA-type glutamate receptors in a rat models of SAS created by 2 weeks of intermittent hypoxic exposure.

Academic Significance and Societal Importance of the Research Achievements

本研究では、中枢神経系の長期増強の発現に関わるAMPA受容体が頸動脈小体の化学受容細胞に発現することを示した。これまでの研究と組み合わせると、化学受容細胞が検出した情報を中枢へ伝えるのみと考えられてきた感覚神経終末がグルタミン酸を分泌し、NMDA型およびAMPA型グルタミン酸受容体を介して化学受容細胞の機能を調節していることが示唆される。今後、頸動脈小体のグルタミン酸受容体が長期増強を制御している事実を捉えることができれば、SASの病態形成に関わる重要な知見を示すことができる。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (11 results)

All 2025 2024 2023

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (5 results)

  • [Journal Article] Immunohistochemical localization of proteins involved in exocytosis of glutamate from P2X3 purinoceptor-expressing subserosal afferent nerve endings in the rat gastric antrum2024

    • Author(s)
      Hirakawa Masato、Yokoyama Takuya、Abdali Sayed Sharif、Yamamoto Yoshio、Saino Tomoyuki
    • Journal Title

      Acta Histochemica

      Volume: 126 Issue: 4 Pages: 152170-152170

    • DOI

      10.1016/j.acthis.2024.152170

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distribution and morphology of serotonin transporter-immunoreactive type I cells in the rat carotid body2024

    • Author(s)
      Yokoyama Takuya、Abdali Sayed Sharif、Nakamuta Nobuaki、Yamamoto Yoshio
    • Journal Title

      The Anatomical Record

      Volume: - Issue: 5 Pages: 1504-1516

    • DOI

      10.1002/ar.25575

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunohistochemical localization of P2Y12 purinoceptors in the rat carotid body2024

    • Author(s)
      Yokoyama Takuya、Saino Tomoyuki、Nakamuta Nobuaki、Yamamoto Yoshio
    • Journal Title

      Autonomic Neuroscience

      Volume: 252 Pages: 103158-103158

    • DOI

      10.1016/j.autneu.2024.103158

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] ADP-mediated Modulation of Intracellular Calcium Responses in Chromaffin Cells: The Role of Ectonucleoside Triphosphate Diphosphohydrolase 2 on Rat Adrenal Medulla Function2023

    • Author(s)
      Maesawa Satsuki、Yokoyama Takuya、Sakanoue Wakana、Yamamoto Yoshio、Hirakawa Masato、Shiraishi Hirohisa、Sato Kenichi、Saino Tomoyuki
    • Journal Title

      Journal of Histochemistry & Cytochemistry

      Volume: 72 Issue: 1 Pages: 41-60

    • DOI

      10.1369/00221554231221872

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Distribution of P2X3 purinoceptor-immunoreactive sensory nerve endings in the carotid body of Japanese macaque (Macaca fuscata)2023

    • Author(s)
      Yokoyama Takuya、Hirakawa Masato、Mochizuki Kei、Suzuki Takashi、Nakajima Katsumi、Saino Tomoyuki
    • Journal Title

      Anatomical Science International

      Volume: 99 Issue: 1 Pages: 68-74

    • DOI

      10.1007/s12565-023-00735-5

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunolocalization of vesicular glutamate transporter 2 and exocytosis‐related proteins in afferent nerve endings innervating taste buds in the rat incisive papilla2023

    • Author(s)
      Yokoyama Takuya、Ito Motoi、Yamamoto Yoshio、Hirakawa Masato、Sakanoue Wakana、Sato Kenichi、Saino Tomoyuki
    • Journal Title

      Anatomia, Histologia, Embryologia

      Volume: - Issue: 4 Pages: 531-537

    • DOI

      10.1111/ahe.12911

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Presentation] ラット頸動脈小体において特徴的な形態を示すセロトニントランスポーター免疫反応性細胞2025

    • Author(s)
      横山拓矢, 中牟田信明, 山本欣郎
    • Organizer
      第130回日本解剖学会_第102回日本生理学会_第98回日本薬理学会合同大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Immunohistochemical localization of proteins involved in purinergic signaling in the rat carotid body2024

    • Author(s)
      Takuya Yokoyama, Nobuaki Nakamuta, Yoshio Yamamoto
    • Organizer
      The 9th Congress of the Asian Association of Veterinary Anatomists
    • Related Report
      2024 Annual Research Report
  • [Presentation] ラット副腎髄質における細胞外ATP分解酵素NTPDase2の発現2023

    • Author(s)
      前澤五月, 横山拓矢, 坂野上和奏, 平川正人, 佐藤健一, 齋野朝幸
    • Organizer
      第51回日本歯科麻酔学会総会・学術集会 第14回アジア歯科麻酔学会連合学術大会
    • Related Report
      2023 Research-status Report
  • [Presentation] ラット切歯乳頭の味蕾における小胞型グルタミン酸輸送体および開口放出関連蛋白の局在2023

    • Author(s)
      横山拓矢, 平川正人, 齋野朝幸, 山本欣郎
    • Organizer
      第166回日本獣医学会学術集会
    • Related Report
      2023 Research-status Report
  • [Presentation] ラット副腎髄質における細胞外ATP分解酵素NTPDase2の局在およびADPによるクロム親和性細胞の興奮調節2023

    • Author(s)
      横山拓矢, 前澤五月, 山本欣郎, 平川正人, 佐藤健一, 齋野朝幸
    • Organizer
      日本解剖学会第69回東北・北海道連合支部学術集会
    • Related Report
      2023 Research-status Report

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Published: 2022-04-19   Modified: 2026-01-16  

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