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Neural mechanisms of spinal cord-to-brain feedback in the regulation of male sexual behavior.

Research Project

Project/Area Number 20K15837
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 44040:Morphology and anatomical structure-related
Research InstitutionOkayama University (2023)
Kanagawa University (2020-2022)

Principal Investigator

Oti Takumi  岡山大学, 理学部, 非常勤研究員 (00837180)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsガストリン放出ペプチド / 腰髄-視床路 / 男性性機能 / 視床室傍核後部 / 視床室傍核 / 腰髄視床路(LSt)ニューロン / Cre-loxP組換え / AAV / 性機能 / オキシトシン受容体 / 性行動 / 脳-脊髄神経ネットワーク
Outline of Research at the Start

雄の性行動を調節する神経ネットワークにおいて、間脳視床・視床下部領域には末梢からの体性感覚信号が入力するが、その神経ネットワークや行動制御メカニズムは不明である。脊髄に存在するガストリン放出ペプチド(GRP)ニューロン系は脊髄レベルで雄の性機能を制御するが、脳との機能連関には不明な点が多い。本研究では、雄の性行動制御メカニズムに着目し、脊髄GRPニューロンの視床・視床下部領域への投射先とその制御メカニズムを解析し、末梢からの感覚を脳へ伝えるフィードバック神経ネットワークとその性行動調節メカニズムを明らかにする。本研究により、心因性の勃起障害や性依存症などの心因性の性機能障害の病態解明を目指す。

Outline of Final Research Achievements

We previously reported that oxytocin projections originating from paraventricular nucleus of hypothalamus to spinal cord activate the spinal gastrin-releasing peptide (GRP) neuron system, which regulates male sexual function at the spinal level, and then facilitate male sexual behavior. On the other hand, the feedback mechanisms that convey the completion of sexual behavior from the spinal cord to the brain were not known. In this project, the projection of spinal GRP neurons to the brain and the localization of GRP receptor-expressing neurons at the projection site have been used to explore the spinal cord to brain neural network. As a result, a novel neural network was found in which spinal GRP neurons project to GRP receptor neurons in the paraventricular nucleus of the thalamus and transmit ejaculatory information to the brain.

Academic Significance and Societal Importance of the Research Achievements

動物の行動は、行動欲求(モチベーション)が高まり、それに伴って脊髄や運動器が制御される。しかし、動物が行動を起こした後、その終了はどのように定義されるのか?モチベーションを鎮めるシグナルはどんなものか?はよくわかっていなかった。そのため、雄の性行動を調節する脳-脊髄神経ネットワークの全容を解明することで、行動の起こりから終了までを一貫して理解し、モチベーションに関わる中枢と運動機能に関わる末梢とをつなぐ脊髄神経ネットワークを明らかにできると考えている。このような研究は将来、家畜や絶滅危惧種の繁殖、あるいは心因性の性機能障害の病態解明・治療法開発につながると考えている。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (17 results)

All 2024 2023 2022 2021 2020

All Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (8 results) (of which Invited: 3 results)

  • [Journal Article] Neuropeptidergic control circuits in the spinal cord for male sexual behaviour: Oxytocin?gastrin‐releasing peptide systems2023

    • Author(s)
      Oti Takumi、Sakamoto Hirotaka
    • Journal Title

      Journal of Neuroendocrinology

      Volume: 35 Issue: 9 Pages: 1-9

    • DOI

      10.1111/jne.13324

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of the expression of gastrin‐releasing peptide and its receptor in the trigeminal and spinal somatosensory systems of Japanese macaque monkeys: Insight into humans2022

    • Author(s)
      Takanami Keiko、Oti Takumi、Kobayashi Yasuhisa、Hasegawa Koki、Ito Takashi、Tsutsui Naoaki、Ueda Yasumasa、Carstens Earl、Sakamoto Tatsuya、Sakamoto Hirotaka
    • Journal Title

      Journal of Comparative Neurology

      Volume: 530 Issue: 16 Pages: 2804-2819

    • DOI

      10.1002/cne.25376

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The gastrin-releasing peptide/bombesin system revisited by a reverse-evolutionary study considering Xenopus2021

    • Author(s)
      Hirooka Asuka、Hamada Mayuko、Fujiyama Daiki、Takanami Keiko、Kobayashi Yasuhisa、Oti Takumi、Katayama Yukitoshi、Sakamoto Tatsuya、Sakamoto Hirotaka
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 13315-13315

    • DOI

      10.1038/s41598-021-92528-x

    • NAID

      120007120048

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sexual Experience Induces the Expression of Gastrin-Releasing Peptide and Oxytocin Receptors in the Spinal Ejaculation Generator in Rats2021

    • Author(s)
      Oti Takumi、Ueda Ryota、Kumagai Ryoko、Nagafuchi Junta、Ito Takashi、Sakamoto Tatsuya、Kondo Yasuhiko、Sakamoto Hirotaka
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 19 Pages: 10362-10362

    • DOI

      10.3390/ijms221910362

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunoelectron Microscopic Characterization of Vasopressin-Producing Neurons in the Hypothalamo-Pituitary Axis of Non-Human Primates by Use of Formaldehyde-Fixed Tissues Stored at ?25 °C for Several Years2021

    • Author(s)
      Otubo Akito、Maejima Sho、Oti Takumi、Satoh Keita、Ueda Yasumasa、Morris John F.、Sakamoto Tatsuya、Sakamoto Hirotaka
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 17 Pages: 9180-9180

    • DOI

      10.3390/ijms22179180

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxytocin Influences Male Sexual Activity via Non-synaptic Axonal Release in the Spinal Cord2021

    • Author(s)
      Oti Takumi、Satoh Keita、Uta Daisuke、Nagafuchi Junta、Tateishi Sayaka、Ueda Ryota、Takanami Keiko、Young Larry J.、Galione Antony、Morris John F.、Sakamoto Tatsuya、Sakamoto Hirotaka
    • Journal Title

      Current Biology

      Volume: 31 Issue: 1 Pages: 103-114

    • DOI

      10.1016/j.cub.2020.09.089

    • NAID

      120007168224

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Systemic effects of oxytocin on male sexual activity via the spinal ejaculation generator in rats2021

    • Author(s)
      Oti Takumi、Sakamoto Tatsuya、Sakamoto Hirotaka
    • Journal Title

      Communicative & Integrative Biology

      Volume: 14 Issue: 1 Pages: 55-60

    • DOI

      10.1080/19420889.2021.1902056

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In Vivo Electrophysiology of Peptidergic Neurons in Deep Layers of the Lumbar Spinal Cord after Optogenetic Stimulation of Hypothalamic Paraventricular Oxytocin Neurons in Rats2021

    • Author(s)
      Uta Daisuke、Oti Takumi、Sakamoto Tatsuya、Sakamoto Hirotaka
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 7 Pages: 3400-3400

    • DOI

      10.3390/ijms22073400

    • NAID

      120007029875

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Variation of pro‐vasopressin processing in parvocellular and magnocellular neurons in the paraventricular nucleus of the hypothalamus: Evidence from the vasopressin‐related glycopeptide copeptin2020

    • Author(s)
      Kawakami Natsuko、Otubo Akito、Maejima Sho、Talukder Ashraf H.、Satoh Keita、Oti Takumi、Takanami Keiko、Ueda Yasumasa、Itoi Keiichi、Morris John F.、Sakamoto Tatsuya、Sakamoto Hirotaka
    • Journal Title

      Journal of Comparative Neurology

      Volume: 529 Issue: 7 Pages: 1372-1390

    • DOI

      10.1002/cne.25026

    • NAID

      120006890023

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Paraventricular oxytocin-spinal gastrin-releasing peptide neuron system controlling male sexual behavior via non-synaptic axonal release2024

    • Author(s)
      Takumi Oti
    • Organizer
      14th WORLD CONGRESS on NEUROHYPOPHYSIAL HORMONES
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 間脳オキシトシン-脊髄ガストリン放出ペプチド系による性行動調節メカニズム2023

    • Author(s)
      越智拓海
    • Organizer
      第49回日本神経内分泌学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] オキシトシンによる脊髄射精中枢を介した男性性機能の調節メカニズム2022

    • Author(s)
      越智拓海,坂本竜哉,坂本浩隆
    • Organizer
      第32回日本性機能学会中部総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 雄の性機能を司る脳-脊髄神経ネットワークと性経験2022

    • Author(s)
      越智拓海
    • Organizer
      日本動物学会第93回早稲田大会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] オキシトシン放出を調節する1回膜貫通型タンパク質CD38のはたらき2022

    • Author(s)
      坂本浩隆、越智拓海、大坪秋人、川上奈津子、ニエンタンフォン、坂本竜哉
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 雄ラット扁桃体内側核後背側部・ガストリン放出ペプチド系は性機能制御と性的モチベーションの両方へ関与するか?2021

    • Author(s)
      高松 廉、上田涼太、大坪秋人、大野智輝、前嶋 翔、越智拓海、 犬束 歩、尾仲達史、坂本竜哉、坂本浩隆
    • Organizer
      第34回日本行動神経内分泌研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] 雄ラット扁桃体内側核後背側部におけるガストリン放出ペプチド系を介した性行動調節メカニズムの解明2021

    • Author(s)
      大坪秋人、上田涼太、高松 廉、大野智輝、前嶋 翔、越智拓海、 犬束 歩、尾仲達史、坂本竜哉、坂本浩隆
    • Organizer
      第47回日本神経内分泌学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 雄ラット視床下部腹内側核オキシトシン受容体ニューロン系による食欲と性欲のスイッチング機構2021

    • Author(s)
      立石沙也加、上田涼太、永渕詢大、越智拓海、犬束 歩、尾仲達史、 Valery Grinevich、坂本竜哉、坂本浩隆
    • Organizer
      第47回日本神経内分泌学会学術集会
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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