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Analysis of delayed neuronal developmental disorder using ASD model animals

Research Project

Project/Area Number 17K01354
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionToyohashi University of Technology

Principal Investigator

Yoshida Sachiko  豊橋技術科学大学, 工学(系)研究科(研究院), 講師 (40222393)

Co-Investigator(Kenkyū-buntansha) 穂積 直裕  豊橋技術科学大学, 工学(系)研究科(研究院), 教授 (30314090)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords発達神経障害 / 動物モデル / 小脳 / バルプロ酸 / グリホサート / ミクログリア / 自閉症 / サイトカイン / 発達器神経障害 / ADHD / 妊娠期ストレス / BDNF / Reelin
Outline of Final Research Achievements

We investigated the delayed neurodegeneration effects of embryonic administration of valproate (VPA), trichostatin A (TSA), Chlorpyrifos (CPF), lipopolysaccharide (LPS) and glyphosate (GLY) which are candidates of inducers for ASD or neuronal disorders. VPA- and TSA-admin. offspring showed the suppression of programmed cell death, while CPF-, LPS- and GLY-ones showed extra neuronal death in developing cerebellar cortex. This enhancement or suppression of neuronal cell death was deeply related to the increase or decrease of inflammatory cytokines, respectively. GLY-admin. offspring showed a transient increase of inflammatory cytokines. VPA-, TSA- and LPS-admin. offspring showed extra foldings of cerebellar lobules. The behavior of VPA-admin. offspring was similar to ADHD, whereas the behavior of GLY-admin. ones was similar to ASD. Postnatal oxytocin administration to VPA-admin. offspring or butyrate administration to GLY-admin. ones reduced their neuronal degeneration.

Academic Significance and Societal Importance of the Research Achievements

自閉症などの発達神経障害は近年増加の傾向があり、社会問題として捉えられている。最近になり、これらが小脳の病変であること、胎生期の化学物質曝露やストレスが影響することが知られてきた。本研究では化学物質誘発性の遅発性神経障害ラットを作成し、化学物質が神経死、あるいは発達過程で削除されるはずの神経の過剰生存を引き起こす機序について研究を進めた。化学物質の作用の特性を知ることで、神経障害を回復させる可能性を示した。

Report

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

    (38 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (13 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 13 results,  Open Access: 3 results) Presentation (23 results) (of which Int'l Joint Research: 12 results)

  • [Int'l Joint Research] City University of New York/Mt. Sinai Hospital(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] New York City University/Mt Sinai Hospital(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Three-dimensional acoustic impedance mapping of cultured biological cells2019

    • Author(s)
      Hozumi N, Yoshida S, Kobayashi K
    • Journal Title

      Ultrasonics

      Volume: 99 Pages: 105966-105966

    • DOI

      10.1016/j.ultras.2019.105966

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hyaluronan synthesis supports glutamate transporter activity2019

    • Author(s)
      Hayashi MK, Nishioka T, Shimizu H, Takahashi K, Kakegawa W, Mikami T, Hirayama Y, Koizumi S, Yoshida S, Yuzaki M, Tammi M, Sekino Y, Kaibuchi K, Shigemoto-Mogami Y, Yasui M, Sato K.
    • Journal Title

      Journal of Neurochemistry

      Volume: 150 Issue: 3 Pages: 249-263

    • DOI

      10.1111/jnc.14791

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Influence of in utero exposure to maternal depression and natural disaster-related stress on infant temperament at 6 months: The children of Superstorm Sandy2019

    • Author(s)
      Nomura Y, Davey K, Pehme PM, Finik J, Glover V, Zhang W, Huang Y, Buthmann J, Dana K, Yoshida S, Tsuchiya KJ, Li XB, Ham J
    • Journal Title

      Infantile Mental Health Journal

      Volume: - Issue: 2 Pages: 204-216

    • DOI

      10.1002/imhj.21766

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 3D音響インピーダンス顕微鏡観察のための皮膚ファントム試料の作製2019

    • Author(s)
      仲田しずか, 東山まりん, 居森厚志, Inna Seviaryna, Roman Maev, 穂積直裕, 吉田祥子
    • Journal Title

      IEICE technical report

      Volume: 119 Pages: 27-30

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tributyltin Inhibits Neural Induction of Human Induced Pluripotent Stem Cells2018

    • Author(s)
      Yamada Shigeru、Kubo Yusuke、Yamazaki Daiju、Sekino Yuko、Nomura Yoko、Yoshida Sachiko、Kanda Yasunari
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 12155-12155

    • DOI

      10.1038/s41598-018-30615-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reaction assessment of cultured breast cancer cells exposed to anti-cancerous agents by means of micro-scale acoustic impedance profile2018

    • Author(s)
      RH Rahayu, K Takanashi, Tiong, I Seviaryna, R Maev, K Kobayashi, N Hozumi, S Yoshida
    • Journal Title

      Japanese Journal of Applied Physics

      Volume: 57 Issue: 7S1 Pages: 07LF26-07LF26

    • DOI

      10.7567/jjap.57.07lf26

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prenatal exposure to valproic acid alters the development of excitability in the postnatal rat hippocampus2018

    • Author(s)
      Yukiko Fueta, Yuko Sekino, Sachiko Yoshida, Yasunari Kanda, Susumu Ueno
    • Journal Title

      NeuroToxicology

      Volume: 65 Pages: 1-8

    • DOI

      10.1016/j.neuro.2018.01.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Timing of Prenatal Exposure to Trauma and Altered Placental Expressions of HPA- Axis Genes and Genes Driving Neurodevelopment2018

    • Author(s)
      Wei Zhang, Qian Li, Maya Deyssenroth, Luca Lambertini, Jackie Finik, Jacob Ham, Yongling Huang, Kenji J Tsuchiya, Patricia Pehme, Jessica Buthmann, Sachiko Yoshida, Jia Chen, Yoko Nomura
    • Journal Title

      J. Neuroendocrinology

      Volume: 30(4) Issue: 4

    • DOI

      10.1111/jne.12581

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Optical measurement of glutamate in slice preparations of the mouse retina2018

    • Author(s)
      M. Ohkuma, M. Kaneda, S. Yoshida, A. Fukuda, E. Miyachi
    • Journal Title

      Neuroscience Research

      Volume: 印刷中 Pages: 30544-8

    • DOI

      10.1016/j.neures.2018.03.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influence of in-utero exposure to maternal depression and natural disaster-related stress on infant temperament at 6 months: The children of Superstorm Sandy.2018

    • Author(s)
      Nomura Y, Davey K, Pehme PM, Finik J, Glover V, Zhang W, Haung M, Buthmann J, Dana K, Yoshida SC, Tsuchiya KJ, Li XB, Ham J.
    • Journal Title

      Infants Mental Health Journal

      Volume: 印刷中

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effects of anticancer drugs on glia-glioma brain tumor model characterized by acoustic impedance microscopy2017

    • Author(s)
      TKS Tiong, TW Chean, H Yamada, K Takahashi, N Hozumi, K Kobayashi, S Yoshida
    • Journal Title

      Japanese Journal of Applied Physics

      Volume: 56 Issue: 7S1 Pages: 07JF15-07JF15

    • DOI

      10.7567/jjap.56.07jf15

    • NAID

      210000148077

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Quantitative evaluation method for differentiation of C2C12 myoblasts by ultrasonic microscopy2017

    • Author(s)
      K Takanashi, M Washiya, K Ota, S Yoshida, N Hozumi, K Kobayashi
    • Journal Title

      Japanese Journal of Applied Physics

      Volume: 56 Issue: 7S1 Pages: 07JF11-07JF11

    • DOI

      10.7567/jjap.56.07jf11

    • NAID

      210000148073

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mutual conversion between B-mode image and acoustic impedance image2017

    • Author(s)
      Tan Wei Chean, Naohiro Hozum, Sachiko Yoshida, K Kobayashi, Yuki Ogura
    • Journal Title

      Japanese Journal of Applied Physics

      Volume: 56 Issue: 7S1 Pages: 07JF18-07JF18

    • DOI

      10.7567/jjap.56.07jf18

    • NAID

      210000148080

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Multi-layered phantoms mimicking skin pathologies for high-resolution ultrasound2020

    • Author(s)
      Inna Seviaryna; Shizuka Nakada; Sachiko Yoshida; Naohiro Hozumi; Roman Gr. Maev
    • Organizer
      SPIE MEDICAL IMAGING
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The epigenetic change of granule cell precursors causes excess folding of cerebellar lobules to induce ASD-like malformation2019

    • Author(s)
      Yoshida Sachiko; Fukushima Midori; Kanda Yasunari
    • Organizer
      EMBL Symposium: Metabolism Meets Epigenetics
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Developmental neurotoxicity and immune abnormality of in-utero food-restriction on rat animal model2019

    • Author(s)
      Yoshida Sachiko; Nomura Yoko; Kanda Yasunari
    • Organizer
      World Congress on Inflammation 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Developmental abnormality induced LPS, bacteria-derived inflammatory agent in rat cerebellar cortex2019

    • Author(s)
      Haruko Ohtsuka; Noriyuki Asai; Thomas Tiong Kwong Soon; Yasunari Kanda; Sachiko Yoshida
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Glial modification in developing VPA-induced ASD model rat cerebellum2019

    • Author(s)
      Midori Fukushima; Chihiro Nishikawa; Yoko Nomura; Yukiko Fueta; Susumu Ueno; Yuko Sekino; Yasunari Kanda; Sachiko Yoshida
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Alteration of cerebellar developmental structures and metabolic condition in prenatal famine rat2019

    • Author(s)
      Kana Miyamoto; Thomas Tiong Kwong Soon; Seta Sato; Yoko Nomura; Yasunari Kanda; Sachiko Yoshida
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Behavioral alteration of chemical-induced autistic model rat and its neuronal mechanism2019

    • Author(s)
      Rie Matsufusa; Yasunari Kanda; Sachiko Yoshida
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Potentiation of developmental neurotoxicity of broad-applied herbicide, Glyphosate2019

    • Author(s)
      Ken Futagami, Huang Yong Lin, Yoko Nomura, Yasunari Kanda, Naohiro Hozumi, Sachiko Yoshida
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 胎児期の LPS 曝露がラットの小脳発達に与える影響2019

    • Author(s)
      大塚暖子; 常本和伸; 諫田泰成; 吉田祥子
    • Organizer
      日本薬学会レギュラトリーサイエンス部会 第5回 次世代を担う若手のためのレギュラトリーサイエンスフォーラム
    • Related Report
      2019 Annual Research Report
  • [Presentation] Developmental neurotoxicity and immune abnormality of in-utero exposure of environmental materials and stress on rat animal model2019

    • Author(s)
      Yoshida S., Fueta Y., Ueno S., Sekino Y., Nomura Y., Kanda Y.
    • Organizer
      FAOPS2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Alteration of gut microbiota and cerebellar structures in Glyphosate-exposure rat2019

    • Author(s)
      Kana Miyamoto, Ken Futagami, Thomas Tiong Kwon Soon, Yuu Hirose, Jianzhong Hu, Yoko Nomura, Yasunari Kanda, Sachiko Yoshida
    • Organizer
      FAOPS2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Altered gut flora and cerebellar development abnormalities in VPA rat model of ASD2019

    • Author(s)
      Thomas Tiong Kwong Soon, Seta Sato, Kana Miyamoto, Yuu Hirose, Yasunari Kanda, Sachiko Yoshida 
    • Organizer
      FAOPS2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The malformation of Purkinje cells becomes the sensing tool for developmental neurotoxicity; its potential and limitation2018

    • Author(s)
      S. Yoshida, S. Iwamoto, Y. Fueta, S. Ueno, Y. Sekino, Y. Nomura, Y. Kanda
    • Organizer
      EUROTOX 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Autistic neuronal differentiation factors derived from astrocyte and microglia: Variant differentiation of cultured neurosphere in Valproate-treated glia-conditioned medium2018

    • Author(s)
      Nishikawa Chihiro, Sato Kaoru, Sekino Yuko, Hozumi Naohiro, Kanda Yasunari, Yoko Nomura, Yoshida Sachiko
    • Organizer
      Neuroscience 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Non-invasive intracellular observation of cancer cells associated with proliferation2018

    • Author(s)
      Thomas Tiong Kwong Soon, Rahma Rahayu Hutami, Kyouichi Takanashi, Naohiro Hozumi, Sachiko Yoshida, Kazuto Kobayashi
    • Organizer
      2018 IEEE IUS Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Microglia activation related to neuronal malformation in developing cerebellar cortex of drug-induced autistic model rat2018

    • Author(s)
      Sachiko Yoshida, Naohiro Hozumi, Yukiko Fueta, Susumu Ueno, Yoko Sekino, Yasunari Kanda
    • Organizer
      Keystone symposia:New Frontiers in Neuroinflammation: What Happens When CNS and Periphery Meet?
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Altered gut microbiota observed in valproate-administrated autistic model rats2018

    • Author(s)
      TKS Tiong, C Nishikawa, Y Fueta, S Ueno, Y Sekino, Y Kanda, Y Nomura, S Yoshida
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Recovery effects with bumetanide or oxytocin administration in developing cerebellar cortex of drug-induced autistic model rat2017

    • Author(s)
      S. Yoshida , K. Ikai, S. Nakajima, Y. Fueta, S. Ueno, N. Hozumi, Y. Sekino, Y. Kanda
    • Organizer
      Neuroscience 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Structural and functional alteration of developing rat cerebellum by administration of autism-inducing drugs2017

    • Author(s)
      Yoshida, S. Fueta, Y Ueno, S Hozumi, N Sekino, Y Kanda, Y
    • Organizer
      10th DOHaD world congress
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Structural and functional alteration of developing rat cerebellum by administration of autism-inducing developing neurotoxins2017

    • Author(s)
      吉田 祥子
    • Organizer
      第60回日本神経化学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 成熟した自閉症モデルラットにおける小脳構造の成熟依存的変化2017

    • Author(s)
      岩本 早起、冨田達郎、中嶋さりい、笛田 由紀子、上野晋、関野裕子、R Maev、穂積直裕、吉田祥子
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Alteration of neurotransmitter release in cerebellar cortex of Valproate-administrated Autistic model rat2017

    • Author(s)
      三上 哲理, 笛田 由紀子, 上野 晋, 関野 祐子, 諫田 泰成, 穂積 直裕, 吉田 祥子
    • Organizer
      第60回日本神経化学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Alteration of GABA release in developing cerebellar cortex of VPA-administrated autistic model rat2017

    • Author(s)
      宮本 佳菜, 三上 哲理, 笛田 由紀子, 上野 晋, 関野 祐子, 諫田 泰成, 穂積 直裕, 吉田 祥子
    • Organizer
      第60回日本神経化学会大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-02-21  

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