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Neural mechanism for recurring of abuse

Research Project

Project/Area Number 17K19922
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Health science and related fields
Research InstitutionNara Medical University

Principal Investigator

Nishi Mayumi  奈良県立医科大学, 医学部, 教授 (40295639)

Co-Investigator(Kenkyū-buntansha) 堀井 謹子  奈良県立医科大学, 医学部, 講師 (80433332)
Project Period (FY) 2017-06-30 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords記憶の痕跡 / 光遺伝学 / 幼児虐待 / c-fos遺伝子プロモーター / ストレス / 母子分離 / 虐待の連鎖 / オプトジェネテイクス / c-Fos / 養育行動
Outline of Final Research Achievements

We investigated whether the memory of maternal separation (MS) during early life is recalled. In order to address this issue, we tried to manipulate the memory engram induced by MS by irreversibly labeling the activated neurons during MS and re-activate these neurons by using optogenetic method. Furthermore, we analyzed maternal behaviors in the offspring suffered from MS. We found that these female offspring showed disorder of maternal behaviors including nest making, retrieving, etc., which caused higher death rate (more than 85%) in the neonatal period than control group.

Academic Significance and Societal Importance of the Research Achievements

本研究では、母子分離を受けたメスマウスが将来母親になった場合に、記憶の痕跡の残された神経細胞をオプトジェネテイクスで特異的に刺激して子育て行動が変化するかを解析し、子育て行動が劣化するならば、「虐待は繰り返される」と言われていた概念の神経基盤を明らかにすることをめざした。最終的にオプトジェネテイクスによる神経細胞の操作にまでは至らなかったが、母子分離を受けたメスマウスが将来母親になった際に子育て行動が低下することを示した。この結果は、虐待のニュースが毎日のように報じられる現代社会において、喫緊に解決すべき課題の解明に繋がるものと考える。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (50 results)

All 2021 2020 2019 2018 2017 2016

All Journal Article (17 results) (of which Peer Reviewed: 17 results,  Open Access: 9 results,  Acknowledgement Compliant: 4 results) Presentation (31 results) (of which Int'l Joint Research: 5 results,  Invited: 3 results) Book (2 results)

  • [Journal Article] The effects of maternal separation on behaviours under social-housing environments in adult male C57BL/6 mice2021

    • Author(s)
      Endo Nozomi、Makinodan Manabu、Mannari-Sasagawa Takayo、Horii-Hayashi Noriko、Somayama Nami、Komori Takashi、Kishimoto Toshifumi、Nishi Mayumi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 527-527

    • DOI

      10.1038/s41598-020-80206-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypothalamic perifornical Urocortin-3 neurons modulate defensive responses to a potential threat stimulus2021

    • Author(s)
      Horii-Hayashi Noriko、Nomoto Kensaku、Endo Nozomi、Yamanaka Akihiro、Kikusui Takefumi、Nishi Mayumi
    • Journal Title

      iScience

      Volume: 24 Issue: 1 Pages: 101908-101908

    • DOI

      10.1016/j.isci.2020.101908

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of early-life stress on the brain and behaviors: Implications of early maternal separation in rodents.2020

    • Author(s)
      Nishi M.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21(19) Issue: 19 Pages: 7212-7212

    • DOI

      10.3390/ijms21197212

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Scaffold attachment factor B: distribution and interaction with ERα in the rat brain.2020

    • Author(s)
      Hashimoto Takashi, Kawata M, Hirahara Y, Nishi M, IIno Satoshi, Matsuda Ken Ichi
    • Journal Title

      Histochem Cell Biol

      Volume: 153 Issue: 5 Pages: 27-40

    • DOI

      10.1007/s00418-020-01853-1

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of early life adverse experience on contents of essential trace elements related to the antioxidative system in the adult mouse hippocampus2020

    • Author(s)
      Azuma C, Minami T, Nishi M
    • Journal Title

      Psychology

      Volume: 11 Issue: 02 Pages: 314-32

    • DOI

      10.4236/psych.2020.112020

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] マウス集団内長期行動解析の試み2020

    • Author(s)
      遠藤のぞみ、牧之段学、西真弓
    • Journal Title

      Medical Sci Digest

      Volume: 46 Pages: 4-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of social behaviors in BTBR T+ Itpr3tf/J mouse model of Autism Spectrum Disorders under social-housing conditions by the Multiple Animals Positioning System2019

    • Author(s)
      Endo N, Makinodan M*, Somayama N, Komori T, Kishimoto T, Nishi M
    • Journal Title

      Experimental Animals

      Volume: 68 Pages: 319-330

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 性ホルモンと脳機能2019

    • Author(s)
      西真弓
    • Journal Title

      分子精神医学

      Volume: 19 Pages: 2-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterization of behavioral phenotypes in the BTBR <i>T<sup>+</sup> Itpr3<sup>tf</sup></i>/J mouse model of autism spectrum disorder under social housing conditions using the multiple animal positioning system2019

    • Author(s)
      Endo N, Makinodan M*, Somayama N, Komori T, Kishimoto T, Nishi M*
    • Journal Title

      Experimental Animals

      Volume: 68 Issue: 3 Pages: 319-330

    • DOI

      10.1538/expanim.18-0177

    • NAID

      130007689880

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple animal positioning system shows that socially-reared mice influence the social proximity of isolation-reared cagemates.2018

    • Author(s)
      Endo N, Ujita W, Fujiwara T, Miyauchi H, Mishima H, Makino Y, Hashimoto L, Oyama, H, Makinodan M, Nishi M, Tohyama C, Kakeyama M*
    • Journal Title

      Communications Biology

      Volume: 1 Issue: 1 Pages: 225-225

    • DOI

      10.1038/s42003-018-0213-5

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Newly Defined Area of the Mouse Anterior Hypothalamus Involved in Septohypothalamic Circuit: Perifornical Area of the Anterior Hypothalamus, PeFAH2018

    • Author(s)
      Nishi M* and Horii-Hayashi N
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 51 Issue: 1 Pages: 1-8

    • DOI

      10.1267/ahc.17030

    • NAID

      130006405036

    • ISSN
      0044-5991, 1347-5800
    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Insights from extracellular matrix studies in the hypothalamus: structural variations of perineuronal nets and discovering a new perifornical area of the anterior hypothalamus.2017

    • Author(s)
      Horii-Hayashi N*,Sasagawa T,Nishi M
    • Journal Title

      Anatomical Science International

      Volume: 92 Issue: 1 Pages: 18-24

    • DOI

      10.1007/s12565-016-0375-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Effects of early life adverse experiences on the brain: implications from maternal separation2017

    • Author(s)
      Nishi M*, Sasagawa T, Horii-Hayashi N
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 149 Issue: 2 Pages: 72-75

    • DOI

      10.1254/fpj.149.72

    • NAID

      130005306339

    • ISSN
      0015-5691, 1347-8397
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Detection of Nitric Oxide Induced by Angiotensin II Receptor Type 1 Using Soluble Guanylate Cyclase beta1 Subunit Fused to a Yellow Fluorescent Protein, Venus.2017

    • Author(s)
      Tsuji Y, Ozawa K*, Komatsubara T, Zhao J, Nishi M, Yoshizumi M
    • Journal Title

      J Fluoresc

      Volume: 27 Pages: 399-405

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structural Reconstruction of the Perivascular Space in the Adult Mouse Neurohypophysis during an Osmotic Stimulation.2017

    • Author(s)
      Nishikawa K, Furube E, Morita-Takemura S, Horii-Hayashi N, Nishi M, Miyata S.
    • Journal Title

      J Neuroendocrinol

      Volume: 29 Issue: 2

    • DOI

      10.1111/jne.12456

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Long-term effects of maternal separation on reward seeking and dopamine D1 receptor expression via DNA methylation in female mice.2017

    • Author(s)
      Sasagawa T, Horii-Hayashi N, Okuda A, Hashimoto T, Azuma C, Nishi M*
    • Journal Title

      Neurosci Lett

      Volume: 641 Pages: 33-39

    • DOI

      10.1016/j.neulet.2017.01.025

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats.2016

    • Author(s)
      Okuda A*, Horii-Hayashi N, Sasagawa T, Shimizu T, Shigematsu H, Iwata E, Morimoto Y, Masuda K, Koizumi M, Akahane M, Nishi M, Tanaka Y
    • Journal Title

      J Neurosurgery Spine

      Volume: 26 Issue: 3 Pages: 388-395

    • DOI

      10.3171/2016.8.spine16250

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] マウス反復社会的敗北ストレスが報酬獲得における“やる気”に及ぼす影響2021

    • Author(s)
      西真弓、遠藤のぞみ、杣山奈実
    • Organizer
      第126回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 視床下部ニューロンの新たな機能―潜在的脅威に対する防御行動の調節―2021

    • Author(s)
      堀井謹子、野元謙作、菊水健史、山中彰弘、西真弓
    • Organizer
      第126回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 発達期環境がマウスの集団内行動様式に与える影響2021

    • Author(s)
      遠藤のぞみ、西真弓
    • Organizer
      第126回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] BTBR自閉症モデルマウスの発達期コルチコステロン濃度の検討2020

    • Author(s)
      遠藤のぞみ、牧之段学、西真弓
    • Organizer
      第125回日本解剖学会総会 全国学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Persistent sciatic vein connection with the small saphenous vein and the deep femoral vein.2020

    • Author(s)
      Azuma Cho, Nakano Kouki, Kitagawa Yuuhi, Tukui Akira, Tikayama Yuuka, Hayasi Mayu, Uesaka Hitoki, Suwanai Hiromitu, Higashitani Yuuki, Horii-Hayashi Noriko, Nishi Mayumi
    • Organizer
      第125回日本解剖学会総会 全国学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Perifornical hypothalamic neurons promote risk assessment behavior to a novel object.2020

    • Author(s)
      Horii Noriko, Nomoto Kensaku, Kikusui Takefumi, Nishi Mayumi
    • Organizer
      第125回日本解剖学会総会 全国学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Effects of early life adversity on the brain.2020

    • Author(s)
      Nishi Mayumi
    • Organizer
      第125回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 幼少期ストレスが脳に及ぼす影響. 日本におけるケミカルバイオロジーの新展開2020

    • Author(s)
      西真弓
    • Organizer
      第189委員会 定例会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Persistent sciatic vein connection with the small saphenous vein and the deep femoral vein2020

    • Author(s)
      C. Azuma, K. Nakano, Y. Kitagawa, A. Tukui, Y, Tikayama, M. Hayashi, H. Uesaka, H. Suwanai, Y. Higashitani, N. Horii-Hayashi, M. Nishi
    • 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] Perifornical hypothalamic neurons promote risk assessment behavior to a novel object2020

    • Author(s)
      Horii Noriko, Nomoto Kensuke, Kikusui Takefumi, Nishi Mayumi
    • 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] BTBR自閉症モデルマウスの発達期コルチコステロン濃度の検討2020

    • Author(s)
      遠藤のぞみ、牧之段学、西真弓
    • 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] 幼少期ストレスが脳に及ぼす影響2020

    • Author(s)
      西真弓
    • Organizer
      日本におけるケミカルバイオロジーの新展開第189委員会 定例会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Effects of early life adverse experiences on the brain: Implications from maternal separation in mice2019

    • Author(s)
      Mayumi Nishi
    • Organizer
      China-Japan High-end Forum on Medical and Health Cooperation 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Effects of repeated social defeat stress on effort-based decision-making behavior in mice2019

    • Author(s)
      Nozomi Endo, Nami Somayama, Takashi Komori, Mayumi Nishi
    • Organizer
      第42日本神経科学大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Effects of early life adverse experiences on the brain: implications from maternal separation in mice.2019

    • Author(s)
      T. Sasagawa, N. Horii-Hayashi, N. Endo, ○M. Nishi
    • Organizer
      The Third Sino-Japan Symposium on the frontier of Behavioral Neuroendocrinology.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The effects of repeated-social defeat stress on social behavior and decision-making related to reward acquisition in mice.2019

    • Author(s)
      Nami Somayama, Nozomi Endo, Takashi Komori, Mamiko Okuda, Hitoshi Nozu, Mayumi Nishi
    • Organizer
      The Third Sino-Japan Symposium on the frontier of Behavioral Neuroendocrinology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Characteristics of Mineral Accumulation in the Monkey Lungs.2019

    • Author(s)
      Cho Azuma, Takao Oishi, Yuka Kojima, Shiichiro Oyama, Masafumi Oyama, Takeshi Minami, Mayumi Nishi
    • Organizer
      第124回日本解剖学会総会 ・全国学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] ハイコストハイリターン/ローコストローリターンの選択.2019

    • Author(s)
      杣山奈実、遠藤のぞみ、小森崇史、西真弓
    • Organizer
      第124回日本解剖学会総会 ・ 全国学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Effects of early life stress on reward seeking behaviors.2018

    • Author(s)
      Mayumi Nishi, Nozomi Endo, Takayo Mannari
    • Organizer
      8th Asia Pacific International Congress of Anatomists and 68th Korean Associating of Anatomists.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 視床下部新規領域PeFAH Urocortin3/Enkephalin共発現ニューロンの機能.2018

    • Author(s)
      堀井謹子、○西真弓
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 妊娠中の受動喫煙が子供の摂食行動・嗜好性行動に及ぼす影響の分子基盤の解明.2018

    • Author(s)
      西真弓、遠藤のぞみ、堀井謹子
    • Organizer
      公益財団法人 喫煙科学研究財団第33回平成29年度助成研究発表会
    • Related Report
      2018 Research-status Report
  • [Presentation] Characterization on of usual behaviors under group-housing conditions by the Multiple Animals Positioning System in the BTBR T+ /J mouse model of autism.2018

    • Author(s)
      Nozomi Endo, Manabu Makinodan, Noriko Horii, Nami Somayama, Takashi Komori, Toshifumi Kishimoto, Mayumi Nishi
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Research-status Report
  • [Presentation] うつ病モデルマウスにおける“意欲”の多角的評価2018

    • Author(s)
      杣山奈実、遠藤のぞみ、小森崇史、西真弓
    • Organizer
      第29回日本行動神経内分泌研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] マウス脳におけるペリニューロナルネットの時空間特異的形成:WFA染色による解析.2018

    • Author(s)
      堀井謹子、遠藤のぞみ、笹川誉世、西真弓
    • Organizer
      第59回日本組織細胞化学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 視床下部新規領域 PeFAH の Urocortin3/Enkephalin 共発現ニューロンの機能.2018

    • Author(s)
      堀井謹子、西真弓
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 集団飼育環境における自閉症モデルマウスの行動解析.2018

    • Author(s)
      遠藤のぞみ、牧之段学、堀井謹子、杣山奈実、小森崇史、岸本年史、西真弓
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] マウスにおける胎児期受動喫煙が摂食、情動行動に及ぼす影響2018

    • Author(s)
      蜂谷奈都子、笹川誉世、堀井謹子、遠藤のぞみ、西真弓
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 新規行動解析システムによる社会的集団における自閉症モデルマウスの行動表現型解析2017

    • Author(s)
      遠藤のぞみ、牧之段学、堀井謹子、杣山奈実、小森崇史、岸本年史、西真弓
    • Organizer
      第93回日本解剖学会近畿支部学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Neural networks between a newly identified perifornical area of the anterior hypothalamus and lateral septum: chemogenetic investigations for physiological roles of urocortin3/enkephalin co-expressing neurons.2017

    • Author(s)
      Mayumi Nishi
    • Organizer
      The 12th China-Japan Joint Seminar on Histichemistry and Cytochemistry
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ストレスの神経科学:コルチコステロイド受容体のリアルタイムイメージングから幼少期ストレスの研究まで2017

    • Author(s)
      西真弓
    • Organizer
      第58回日本組織細胞化学会総会・学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Neural circuit controlling defensive active coping with inanimate threats2017

    • Author(s)
      Noriko Horii, Takayo Sasagawa, Mayumi Nishi
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Book] 栄養科学シリーズNEXT 解剖生理学第3版(分担執筆:4.1; 6)2020

    • Author(s)
      西真弓
    • Total Pages
      179
    • Publisher
      講談社サイテイフィク
    • ISBN
      9784065166352
    • Related Report
      2020 Annual Research Report 2019 Research-status Report
  • [Book] スタンフォード神経生物学2017

    • Author(s)
      西真弓 翻訳(分担)
    • Total Pages
      705
    • Publisher
      メディカル・サイエンス・インターナショナル
    • ISBN
      9784895928885
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2022-01-27  

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