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Heterosexual communication and microglial synaptic pruning

Research Project

Project/Area Number 20K21465
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 46:Neuroscience and related fields
Research InstitutionEhime University

Principal Investigator

Tanaka Junya  愛媛大学, 医学系研究科, 教授 (70217040)

Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2021: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2020: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords行動科学 / 恋愛 / ラット / ミクログリア / アドレナリン受容体 / 前頭葉 / シナプス / 社会行動 / 行動実験 / FACS / 前頭前皮質 / cFos / RNAseq / microglia / sexual communication / synaptic pruning / phagocytosis / prefrontal cortex
Outline of Research at the Start

我々は、男女間の恋愛のモチベーションの脳科学的な背景を探るため、ラットを用いた行動実験を行い、オスに好かれないメスは、多動で社会性が低く、不安感が少ないこと、さらに、前頭葉ミクログリアの活性が低いことを見出してきた。本研究では、ミクログリアのシナプス貪食活性と神経細胞活動・行動との関連を明らかにし、ミクログリアに対する種々の薬理学的介入により、メスの恋愛行動を変化させることができることを示す。これによって、社会問題となっている結婚率の低下、晩婚化、人口減少などについて、何らかの提言ができるように研究を進める。

Outline of Final Research Achievements

Recently in many developed countries, love and marriage rates as well as birth rates are declining, and consequently the population has begun to decline. To explore the biological background for these trends, we developed a behavioral test to determine what kinds of female Wistar rats are preferred by males. Male Wistar rats preferred females with high anxiety and low motor activity. We examined the activity of microglia in the prefrontal cortex and found that less active females with higher microglial activity that phagocytosed more synapses, compared to active females with less anxious. Administration of clenbuterol, a β2 agonist that increases microglial activity, and propranolol, a β-blocker that suppresses microglial activity, caused the former to be preferred by males and the latter to be less preferred. These results suggest that male rats prefer inactive female rats and that this is due to enhanced synaptic phagocytosis by microglia.

Academic Significance and Societal Importance of the Research Achievements

近年、先進国では世界的に出生率が減少している。特に、日本では出生率の低下の背景に恋愛率、結婚率の低下が指摘されている。今回の行動実験の結論は、不安感が強くおとなしいメスがオスに好かれるというものであった。特に、明暗箱試験で、巣に相当する暗室に長時間滞在するような行動をとるメスが好かれた。天敵が多数いる野生社会では、巣に長時間母親が滞在する方が子育てに有利であると考えられ、子孫を残す上で有利となるメスをオスが選ぶ傾向があるものと考えられた。人間社会において、女性の社会進出と出生率は反比例する傾向があるが、今回のラットによる実験結果を敷衍できるかどうかさらなる検討が必要である。

Report

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

    (18 results)

All 2022 2021 2020 Other

All Int'l Joint Research (4 results) Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 10 results)

  • [Int'l Joint Research] The University of Manchester(英国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Pittsburgh(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Pittsburgh(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] The University of Manchester(英国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Surgical stress quickly affects the numbers of circulating B-cells and neutrophils in murine septic and aseptic models through a β2 adrenergic receptor2022

    • Author(s)
      Ryutaro Nishioka, Yusuke Nishi, Mohammed E. Choudhury, Riko Miyaike, Ayataka Shinnishi, Kensuke Umakoshi, Yasutsugu Takada, Norio Sato, Mayuki Aibiki, Hajime Yano, Junya Tanaka
    • Journal Title

      Journal of Immunotoxicology

      Volume: 19 Issue: 1 Pages: 8-16

    • DOI

      10.1080/1547691x.2022.2029630

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Insomnia and depressive behavior of MyD88-deficient mice: Relationships with altered microglial functions2022

    • Author(s)
      Mohammed E. Choudhury, Kanta Mikami, Yuiko Nakanishi, Taisei Matsuura, Ryo Utsunomiya, Hajime Yano, Madoka Kubo, Rina Ando, Jun Iwanami, Masakatsu Yamashita, Masahiro Nagai, JunyaTanaka
    • Journal Title

      Journal of Neuroimmunology

      Volume: 363 Pages: 577794-577794

    • DOI

      10.1016/j.jneuroim.2021.577794

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Length impairments of the axon initial segment in rodent models of attention-deficit hyperactivity disorder and autism spectrum disorder2022

    • Author(s)
      Noriyoshi Usui, Xiaoye Tiane, Wakana Harigai, Shogo Togawa, Ryo Utsunomiya, Tomomi Doi, Ko Miyoshi, Koh Shinoda, Junya Tanaka, Shoichi Shimada, Taiichi Katayama, Takeshi Yoshimura
    • Journal Title

      Neurochemistry International

      Volume: 153 Pages: 105273-105273

    • DOI

      10.1016/j.neuint.2021.105273

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microglia and the aging brain: Are geriatric microglia linked to poor sleep quality?2021

    • Author(s)
      Choudhury, M.E., Miyanishi, K., Takeda, H., Tanaka, J.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 15 Pages: 7824-7824

    • DOI

      10.3390/ijms22157824

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chloride intracellular channel protein 2 is secreted and inhibits MMP14 activity, while preventing tumor cell invasion and metastasis2021

    • Author(s)
      Saya Ozaki, Akihiro Umakoshi, Hajime Yano, ............ Junya Tanaka
    • Journal Title

      Neoplasia

      Volume: 23 Issue: 8 Pages: 754-765

    • DOI

      10.1016/j.neo.2021.06.001

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dual Roles of Microglia in the Basal Ganglia in Parkinson’s Disease2021

    • Author(s)
      Mohammed E. Choudhury, Yuka Kigami, Junya Tanaka
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 8 Pages: 3907-3907

    • DOI

      10.3390/ijms22083907

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Snapshot of microglial physiological functions2021

    • Author(s)
      Alexei Verkhratsky, Dandan Sun, Junya Tanaka
    • Journal Title

      Neurochemistry International

      Volume: 144 Pages: 104960-104960

    • DOI

      10.1016/j.neuint.2021.104960

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Microglial metabolic disturbances and neuroinflammation in cerebral infarction2021

    • Author(s)
      Haruna Takeda, Teruaki Yamaguchi, Hajime Yano, Junya Tanaka
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 145 Issue: 1 Pages: 130-139

    • DOI

      10.1016/j.jphs.2020.11.007

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD44 expression in the tumor periphery predicts the responsiveness to bevacizumab in the treatment of recurrent glioblastoma2021

    • Author(s)
      Nishikawa Masahiro、Inoue Akihiro、Ohnishi Takanori、Yano Hajime、Kanemura Yonehiro、Kohno Shohei、Ohue Shiro、Ozaki Saya、Matsumoto Shirabe、Suehiro Satoshi、Nakamura Yawara、Shigekawa Seiji、Watanabe Hideaki、Kitazawa Riko、Tanaka Junya、Kunieda Takeharu
    • Journal Title

      Cancer Medicine

      Volume: 10 Issue: 6 Pages: 2013-2025

    • DOI

      10.1002/cam4.3767

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synaptic elimination by microglia and disturbed higher brain functions2021

    • Author(s)
      Miyanishi Kazuya、Sato Arisa、Kihara Nanako、Utsunomiya Ryo、Tanaka Junya
    • Journal Title

      Neurochemistry International

      Volume: 142 Pages: 104901-104901

    • DOI

      10.1016/j.neuint.2020.104901

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Generation of CSF1-Independent Ramified Microglia-Like Cells from Leptomeninges In Vitro2020

    • Author(s)
      Tanaka J, Takahashi H, Yano H, Nakanishi H.
    • Journal Title

      Cells

      Volume: 10 Issue: 1 Pages: 24-37

    • DOI

      10.3390/cells10010024

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lister hooded rats as a novel animal model of attention-deficit/hyperactivity disorder2020

    • Author(s)
      Jogamoto Toshihiro、Utsunomiya Ryo、Sato Arisa、Kihara Nanako、Choudhury Mohammed E.、Miyanishi Kazuya、Kubo Madoka、Nagai Masahiro、Nomoto Masahiro、Yano Hajime、Shimizu Yusuke I.、Fukuda Mitsumasa、Ishii Eiichi、Eguchi Mariko、Tanaka Junya
    • Journal Title

      Neurochemistry International

      Volume: 141 Pages: 104857-104857

    • DOI

      10.1016/j.neuint.2020.104857

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activated microglia-derived macrophage-like cells exacerbate brain edema after ischemic stroke correlate with astrocytic expression of aquaporin-4 and interleukin-1 alpha release2020

    • Author(s)
      Murata Yukie、Sugimoto Kana、Yang Chihpin、Harada Kazuo、Gono Rina、Harada Teiji、Miyashita Yohei、Higashisaka Kazuma、Katada Ryuichi、Tanaka Junya、Matsumoto Hiroshi
    • Journal Title

      Neurochemistry International

      Volume: 140 Pages: 104848-104848

    • DOI

      10.1016/j.neuint.2020.104848

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microglia and Macrophages in the Pathological Central and Peripheral Nervous Systems2020

    • Author(s)
      Abe N, Nishihara T, Yorozuya T, Tanaka J
    • Journal Title

      Cells

      Volume: 9 Issue: 9 Pages: 2132-2132

    • DOI

      10.3390/cells9092132

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2020-08-03   Modified: 2023-01-30  

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