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Elucidation of mechanisms of developmental neurotoxicity by micro-morphological analysis

Research Project

Project/Area Number 24221003
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Risk sciences of radiation/Chemicals
Research InstitutionUniversity of Tsukuba (2016)
The University of Tokyo (2012-2015)

Principal Investigator

Tohyama Chiharu  筑波大学, 医学医療系, 客員教授 (10150872)

Co-Investigator(Kenkyū-buntansha) 渡辺 知保  東京大学, 医学(系)研究科(研究院), 教授 (70220902)
Co-Investigator(Renkei-kenkyūsha) NAKAJIMA Kazunori  慶應義塾大学, 医学部, 教授 (90280734)
KAKEYAMA Masaki  早稲田大学, 人間科学学術院, 教授 (30353535)
MAEKAWA Fumihiko  国立環境研究所, 環境リクス・健康研究センター, 主任研究員 (40382866)
Research Collaborator KIMURA Eiki  筑波大学, 医学医療系, 研究員 (90710054)
Project Period (FY) 2012-05-31 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥216,840,000 (Direct Cost: ¥166,800,000、Indirect Cost: ¥50,040,000)
Fiscal Year 2016: ¥43,030,000 (Direct Cost: ¥33,100,000、Indirect Cost: ¥9,930,000)
Fiscal Year 2015: ¥43,420,000 (Direct Cost: ¥33,400,000、Indirect Cost: ¥10,020,000)
Fiscal Year 2014: ¥43,420,000 (Direct Cost: ¥33,400,000、Indirect Cost: ¥10,020,000)
Fiscal Year 2013: ¥43,420,000 (Direct Cost: ¥33,400,000、Indirect Cost: ¥10,020,000)
Fiscal Year 2012: ¥43,550,000 (Direct Cost: ¥33,500,000、Indirect Cost: ¥10,050,000)
Keywords発達神経毒性 / 微細形態 / 高次脳機能 / ダイオキシン / ビスフェノールA / ヒ素 / アリール炭化水素受容体 / 内分泌かく乱作用 / 芳香族炭化水素受容体 / 超音波発声 / 認知・行動毒性 / 環境化学物質 / 胎児期起源環境疾患 / 樹状突起 / 軸索 / 細胞移動 / 化学物質曝露
Outline of Final Research Achievements

Perinatal exposure to low-dose environmental chemicals, including dioxin, bisphenol A, and inorganic arsenic, has been shown to induce abnormalities in higher brain function (learning, memory, emotion, and sociality) in humans and laboratory animals.
In the present study, we showed that abnormalities in micro-morphology of neurons (dendrite length and complexity, spine density and so on), as well as abnormal gene expression in some cases, were present at the developing stage of exposed animals, and that ultrasonic vocalization behavior could be a novel toxicity endpoint of brain function of mouse neonates.

Assessment Rating
Verification Result (Rating)

A

Assessment Rating
Result (Rating)

A-: Progress in the research is steadily towards the initial goal. However, further efforts are necessary as a part of the research progress is delayed.

Report

(9 results)
  • 2017 Research Progress Assessment (Verification Result) ( PDF )
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report   Abstract(Research Progress Assessment) ( PDF )   Research Progress Assessment (Result) ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (42 results)

All 2017 2016 2015 2014 2013 2012 Other

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 8 results,  Acknowledgement Compliant: 6 results) Presentation (28 results) (of which Int'l Joint Research: 6 results,  Invited: 5 results) Remarks (2 results)

  • [Journal Article] Excessive activation of AhR signaling disrupts neuronal migration in the hippocampal CA1 region in the developing mouse2017

    • Author(s)
      Eiki Kimura, Ken-ichiro Kubo, Toshihiro Endo, Kazunori Nakajima, Masaki Kakeyama, and Chiharu Tohyama
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 42 Issue: 1 Pages: 25-30

    • DOI

      10.2131/jts.42.25

    • NAID

      130005286645

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Embryonic and postnatal expression of aryl hydrocarbon receptor mRNA in mouse brain2017

    • Author(s)
      Kimura E, Tohyama C
    • Journal Title

      Frontiers in Neuroanatomy

      Volume: 11 Pages: 1-10

    • DOI

      10.3389/fnana.2017.00004

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] AhR signaling activation disrupts migration and dendritic growth of olfactory interneurons in the developing mouse2016

    • Author(s)
      Kimura E, Ding Y, Tohyama C
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 1-11

    • DOI

      10.1038/srep26386

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] In utero and lactational dioxin exposure induces Sema3b and Sema3g gene expression in the developing mouse brain2016

    • Author(s)
      Kimura E, Endo T, Yoshioka W, Ding Y, Ujita W, Kakeyama M, Tohyama C
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 476 Issue: 2 Pages: 108-113

    • DOI

      10.1016/j.bbrc.2016.05.048

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Developmental neurotoxicity test guidelines: problems and perspectives2016

    • Author(s)
      Tohyama C
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 41 Issue: Special Pages: SP69-SP79

    • DOI

      10.2131/jts.41.SP69

    • NAID

      130005399499

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] In utero bisphenol A exposure induces abnormal neuronal migration in the cerebral cortex of mice.2016

    • Author(s)
      Wenting Ling, Toshihiro Endo, Ken-ichiro Kubo, Masaki Kakeyama, Kazunori Nakajima, and Chiharu Tohyama.
    • Journal Title

      Front. Endocrinol.

      Volume: 7 Pages: 7-7

    • DOI

      10.3389/fendo.2016.00007

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice2016

    • Author(s)
      Aung KH, Kyi-Tha-Thu C, Sano K, Nakamura K, Tanoue A, Nohara K, Kakeyama M, Tohyama C, Tsukahara S, Maekawa F
    • Journal Title

      Frontiers in Neuroscience

      Volume: 10 Pages: 1-12

    • DOI

      10.3389/fnins.2016.00137

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Developmental origin of abnormal dendritic growth in the mouse brain induced by in utero disruption of aryl hydrocarbon receptor signaling.2015

    • Author(s)
      Eiki Kimura, Ken-ichiro Kubo, Chieri Matsuyoshi, Seico Benner, Mayuko Hosokawa, Toshihiro Endo, Wenting Ling, Masanobu Kohda, Kazuhito Yokoyama, Kazunori Nakajima, Masaki Kakeyama, and Chiharu Tohyama.
    • Journal Title

      Neurotoxicol. Teratol.

      Volume: 52 Pages: 42-50

    • DOI

      10.1016/j.ntt.2015.10.005

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prenatal exposure to bisphenol A impacts neuronal morphology in the hippocampal CA1 region in developing and aged mice.2015

    • Author(s)
      Kimura E, Matsuyoshi C, Miyazaki W, Benner S, Hosokawa M, Yokoyama K, Kakeyama M, Tohyama C.
    • Journal Title

      Archives of Toxicology

      Volume: in press Issue: 3 Pages: 691-700

    • DOI

      10.1007/s00204-015-1485-x

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Disruption of paired-associate learning in rat offspring perinatally exposed to dioxins2013

    • Author(s)
      Kakeyama M, Endo T, Zang Y, Miyazaki Y, Tohyama C
    • Journal Title

      Archives of Toxicology

      Volume: 88 Pages: 789-98

    • DOI

      10.1007/s00204-013-1161-y

    • NAID

      120006986679

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Executive Function Deficits and Social-Behavioral Abnormality in Mice Exposed to a Low Dose of Dioxin In Utero and via Lactation2012

    • Author(s)
      Endo T, Kakeyama M, Uemura Y, Haijima A, Okuno H, Bito H, Tohyama C
    • Journal Title

      PLOS ONE

      Volume: 7 Issue: 12 Pages: e50741-e50741

    • DOI

      10.1371/journal.pone.0050741

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fluorescence laser microdissection reveals a distinct pattern of gene activation in the mouse hippocampal region2012

    • Author(s)
      Yoshioka W, Endo N, Kurashige A, Haijima A, Endo T, Shibata T, Nishiyama R,Kakeyama M, Tohyama C
    • Journal Title

      Scientific Reports

      Volume: 2 Issue: 1 Pages: 783-783

    • DOI

      10.1038/srep00783

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] In utero and lactational TCDD exposure impairs ultrasonic vocalization of neonatal mice2017

    • Author(s)
      Eiki Kimura, Chiharu Tohyama
    • Organizer
      Society of Toxicology (56th Annual Meeting and ToxExpo)
    • Place of Presentation
      Baltimore Convention Center, Baltimore, Maryland, USA
    • Year and Date
      2017-03-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 周産期ダイオキシン曝露が発達期マウスの神経回路構築に及ぼす影響2016

    • Author(s)
      木村栄輝、遠藤俊裕、吉岡亘、松吉智瑛里、宇治田和佳、掛山正心、遠山千春
    • Organizer
      環境ホルモン学会第19回研究発表会
    • Place of Presentation
      茨城県つくば市(文部科学省研究交流センター)
    • Year and Date
      2016-12-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] Significance of AHR signaling on the mammalian brain development2016

    • Author(s)
      Kimura E, Tohyama C
    • Organizer
      AHR Conference 2016
    • Place of Presentation
      University of Rochester School of Medicine, Rochester, New York, USA
    • Year and Date
      2016-08-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 新生仔マウスの超音波発声を指標とした新たな毒性評価手法の検討2016

    • Author(s)
      木村栄輝、遠山千春
    • Organizer
      第43回日本毒性学会学術年会
    • Place of Presentation
      愛知県名古屋市(ウインクあいち)
    • Year and Date
      2016-06-29
    • Related Report
      2016 Annual Research Report
  • [Presentation] 「環境ホルモン」と毒性学:問題提起から今日まで2016

    • Author(s)
      遠山千春
    • Organizer
      第43回日本毒性学会学術年会
    • Place of Presentation
      愛知県名古屋市(ウインクあいち)
    • Year and Date
      2016-06-29
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Constitutive activation of AhR signaling disrupts dendritic growth and cellular migration of cortical pyramidal neurons in the developing mouse brain2016

    • Author(s)
      Kimura E, Kubo K, Endo T, Ling W, Nakajima K, Kakeyama M, Tohyama C
    • Organizer
      Society of Toxicology (55th Annual Meeting and ToxExpo)
    • Place of Presentation
      New Orleans, Louisiana, USA
    • Year and Date
      2016-03-12
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 発達期大脳皮質ニューロンにおけるAhRシグナル活性化が樹状突起成長と移動距離に及ぼす影響2015

    • Author(s)
      木村栄輝、久保健一郎、遠藤俊裕、凌文てい、仲嶋一範、掛山正心、遠山千春
    • Organizer
      第18回環境ホルモン学会
    • Place of Presentation
      栃木県下野市(自治医科大学)
    • Year and Date
      2015-12-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] AhR activation and TCDD exposure impair dendritic morphology in the developing olfactory bulb2015

    • Author(s)
      Kimura E, Ding Y, Kakeyama M, Tohyama C
    • Organizer
      The 51st Congress of the European Societies of Toxicology
    • Place of Presentation
      Porto, Portugal
    • Year and Date
      2015-09-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 健康環境医工学における毒性学研究の展開2015

    • Author(s)
      遠山千春
    • Organizer
      第42回日本毒性学会学術年会
    • Place of Presentation
      石川県金沢市(石川県立音楽堂、金沢市アートホール、ホテル日航金沢)
    • Year and Date
      2015-06-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 神経細胞におけるAhRシグナルの活性化が発達期の細胞移動および形態に与える影響2015

    • Author(s)
      木村栄輝、丁雲潔、掛山正心、遠山千春
    • Organizer
      第42回日本毒性学会学術年会
    • Place of Presentation
      石川県金沢市(石川県立音楽堂、金沢市アートホール、ホテル日航金沢)
    • Year and Date
      2015-06-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Novel methods to study how environmental factors affect the developing rodent brain2015

    • Author(s)
      Tohyama C
    • Organizer
      The 7th International Congress of Asia Society of Toxicology
    • Place of Presentation
      Jeju island, Korea
    • Year and Date
      2015-06-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Activation of AhR signaling and perinatal TCDD exposure impair neuronal morphology in the developing olfactory bulb2015

    • Author(s)
      Ding Y, Kimura E, Kakeyama M, Tohyama C
    • Organizer
      The 7th International Congress of Asia Society of Toxicology
    • Place of Presentation
      Jeju island, Korea
    • Year and Date
      2015-06-23
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Abnormal neuronal migration and behavior in mice exposed in utero to Bisphenol A2014

    • Author(s)
      Ling W, Endo T, Miyazaki W, Kimura E, Kubo K, Nakajima K, Kakeyama M, and Tohyama C
    • Organizer
      53rd Annual Meeting of the Society of Toxicology and ToxExpo
    • Place of Presentation
      Phoenix, Arizona, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Impact of perinatal TCDD exposure on neuroendocrine stress response system in mice2014

    • Author(s)
      Benner S, Inoshita T, Ding Y, Kakeyama M, and Tohyama C.
    • Organizer
      53rd Annual Meeting of the Society of Toxicology and ToxExpo
    • Place of Presentation
      Phoenix, Arizona, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 周産期化学物質曝露による神経発達毒性・高次脳機能異常の検出手法開発2013

    • Author(s)
      遠山千春、掛山正心
    • Organizer
      第40回 日本毒性学会学術年会
    • Place of Presentation
      千葉県千葉市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 胎仔期ビスフェノールA曝露によるマウス大脳皮質形成障害と衝動行動2013

    • Author(s)
      凌文てい、遠藤俊裕、宮崎航、木村栄輝、久保健一郎、仲嶋一範、掛山正心、遠山千春
    • Organizer
      Neuro2013 (第36回日本神経科学大会)
    • Place of Presentation
      京都府京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] AhRシグナルの活性化は発達期脳における海馬CA1錐体細胞の樹状突起成長を制御している2013

    • Author(s)
      木村栄輝、松吉智瑛里、宮崎航、久保健一郎、遠藤俊裕、凌文てい、仲嶋一範、掛山正心、遠山千春
    • Organizer
      Neuro2013 (第36回日本神経科学大会)
    • Place of Presentation
      京都府京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] マウスにおける行動柔軟性:包括的解析のための新規ハイスループット試験系の開発2013

    • Author(s)
      遠藤俊裕、ベナー聖子、遠藤のぞみ、古瀬民夫、若菜茂晴、梶井靖、David P. Wolfer、Hans-Peter Lipp、遠山千春、掛山正心
    • Organizer
      Neuro2013 (第36回日本神経科学大会)
    • Place of Presentation
      京都府京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Perinatal Exposure to Bisphenol A Affects Cortical Development and Induces Impulsive Behavior in Mice2013

    • Author(s)
      Ling W, Endo T, Miyazaki W, Kimura E, Kubo K, Nakajima K, Kakeyama M, Tohyama C
    • Organizer
      World Federation of Societies of Biological Psychiatry Congress 2013
    • Place of Presentation
      京都府京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Behavioral flexibililty in mice: Development of a novel high-throughput assay for comprehensive analysis applicable to psychiatry research2013

    • Author(s)
      Endo T, Benner S, Endo N, Furuse T, Wakana S, Kajii Y, Wolfer D P, Lipp H P, Tohyama C, Kakeyama M
    • Organizer
      The 11th World Federation of Societies of Biological Psychiatry(第11回世界生物学的精神医学会国際会議)
    • Place of Presentation
      京都府京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Perinatal Exposure to Bisphenol A Affects Cortical Development and Induces Impulsive Behavior in Mice2013

    • Author(s)
      Ling W, Endo T, Miyazaki W, Kimura E, Kubo K, Nakajima K, Kakeyama M, Tohyama M
    • Organizer
      The XIII International Congress of Toxicology
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2013 Annual Research Report
  • [Presentation] Exposure to Bisphenol A during Gestation Alters Neuronal Morphology in the Hippocampus of Mouse Offspring2013

    • Author(s)
      Kimura E, Miyazaki W, Matsuyoshi C, Kakeyama M, Tohyama C
    • Organizer
      The XIII International Congress of Toxicology
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2013 Annual Research Report
  • [Presentation] In utero exposure to Bisphenol A interrupts cerebral cortex development and behavior in mice2013

    • Author(s)
      Ling W, Endo T, Miyazaki W, Kimura E, Kubo K, Nakajima K, Kakeyama M and Tohyama C
    • Organizer
      環境ホルモン学会第16回研究発表会
    • Place of Presentation
      東京大学 (東京都文京区)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 周産期TCDD曝露モデルマウスにおけるストレス応答系への発達毒性影響2013

    • Author(s)
      ベナー聖子, 井下太貴, 丁雲潔, 掛山正心, 遠山千春
    • Organizer
      環境ホルモン学会第16回研究発表会
    • Place of Presentation
      東京大学 (東京都文京区)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 生体組織の微細断片における遺伝子発現測定法の開発2013

    • Author(s)
      倉繁秋江
    • Organizer
      第12回分子予防環境医学研究会
    • Place of Presentation
      つくばサイエンス・インフォメーションセンター 茨城県つくば市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Hippocampal dendritic morphology upon prenatal chemical exposure in mice2012

    • Author(s)
      Kimura E
    • Organizer
      Neuroscience 2012, Society for Neuroscience
    • Place of Presentation
      New Orleans, LA, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] ダイオキシンまたはビスフェノールAの周産期曝露が 産仔マウスの海馬ニューロン微細形態に与える変化2012

    • Author(s)
      木村栄輝
    • Organizer
      第15回環境ホルモン学会研究会
    • Place of Presentation
      東京大学山上会館 東京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] 環境ホルモン研究の現状---低用量影響とエピジェネティックス

    • Author(s)
      遠山千春
    • Organizer
      ダイオキシン・環境ホルモン国民会議講演会
    • Place of Presentation
      エコギャラリー新宿 東京都
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Remarks] 健康環境医工学部門ウェッブサイト

    • URL

      http://env-health.m.u-tokyo.ac.jp/

    • Related Report
      2013 Annual Research Report
  • [Remarks] http://env-health.m.u-tokyo.ac.jp/news.html

    • Related Report
      2012 Annual Research Report

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Published: 2012-11-27   Modified: 2019-07-29  

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