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PGD2 is implicated in neuronal development via DP1 receptor and the over-activation of PGD2-DP1 signaling during early development could be a risk factor for neurodevelopmental disorders

Research Project

Project/Area Number 16K09967
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionOsaka University

Principal Investigator

Mohri Ikuko  大阪大学, 連合小児発達学研究科, 准教授 (70399351)

Co-Investigator(Kenkyū-buntansha) 谷池 雅子  大阪大学, 連合小児発達学研究科, 教授 (30263289)
早田 敦子  大阪大学, 連合小児発達学研究科, 助教 (70390812)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords自閉症 / PGD2 / 造血器型プロスタグランジンD合成酵素 / ミクログリア / マウス / 神経突起 / スパイン / 神経炎症 / プロスタグランジンD2 / プロスタグランジンD合成酵素 / 幼若脳 / 樹状突起 / グリア / 周産期 / プロスタグランジン / シナプス / シナプス形成 / 発現制御 / プロストグランジンD2
Outline of Final Research Achievements

Prostaglandin D2 (PGD2) is an inflammatory mediator. During neuroinflammation, microglia produce hematopoietic PGD synthase (HPGDS). Previously, we found that HPGDS is expressed in activated microglia in the brains of Autism. In this study, we investigated whether PGD2 affects neuronal morphological development. In the primary cultured cortical neurons, PGD2 receptor agonist (DP1 agonist) increased the primary neurite number and total length of dendrites, and immature dendritic spines. In addition, repeated administration of DP1 agonist to the mouse during early postnatal period caused alterations in the dendritic morphology and the number of synapses in the prefrontal cortex. These results suggest that PGD2 is implicated in neuronal development via DP1 receptor and the over-activation of PGD2-DP1 signaling during early development could be a risk factor for autism.

Academic Significance and Societal Importance of the Research Achievements

自閉症は様々な原因で発症することが知られている。近年の報告では60人に1人が自閉症であるとされ、非常に頻度が高い疾患である。近年、周産期の虚血・低酸素などのトラブルが自閉症のリスクファクターであることが報告されている。我々は本研究で周産期イベントで産生されるPGD2が神経形態に影響し、自閉症発症につながることが示された。このことより、PGD2合成酵素阻害剤等、PGD2産生抑制による自閉症発症予防法への展望がひらけ、社会的に大きな意味がある。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (20 results)

All 2019 2018 2017 2016

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 11 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Evaluation of Problem-Solving Training for Children with Autism Spectrum Disorder and Their Mothers.2019

    • Author(s)
      Okuno H, Yamamoto T, Tatsumi A, Mohri I, Taniike M
    • Journal Title

      Japanese Journal of Child and Adolescent Psychiatry.

      Volume: -

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impaired executive function in junior high school students with excess sleep time.2019

    • Author(s)
      Momoda M, Yoshizaki A, Nagatani F, Nishimura T, Taniike M, Mohri I.
    • Journal Title

      Vulnerable Children & Youth Studies.

      Volume: - Issue: 2 Pages: 116-128

    • DOI

      10.1080/17450128.2019.1580404

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Abnormal Cortical Activation During Silent Reading in Adolescents with Autism Spectrum Disorder.2019

    • Author(s)
      Ogawa R, Kagitani-Shimono K, Matsuzaki J, Tanigawa J, Hanaie R, Yamamoto T, Tominaga K, Hirata M, Mohri I, Taniike M
    • Journal Title

      Brain and Development.

      Volume: 41 Issue: 3 Pages: 234-244

    • DOI

      10.1016/j.braindev.2018.10.013

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clasmatodendrosis is associated with dendritic spines and does not represent autophagic astrocyte death in influenza-associated encephalopathy.2019

    • Author(s)
      Tachibana M, Mohri I, Hirata I, Kuwada A, Kimura-Ohba S, Kagitani-Shimono K, Fushimi H, Inoue T, Shiomi M, Kakuta Y, Takeuchi M, Murayama S, Nakayama M, Ozono K, Taniike M
    • Journal Title

      Brain and Development.

      Volume: 41 Issue: 1 Pages: 85-95

    • DOI

      10.1016/j.braindev.2018.07.008

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] White Matter Tract-Cognitive Relationshipsin Children with High-Functioning Autism Spectrum Disorder. Psychiatry Investigation2019

    • Author(s)
      Kato Y, Kagitani-Shimono K, Matsuzaki J, Hanaie R, Yamamoto T, Tominaga K, Watanabe Y, Mohri I, Taniike M.
    • Journal Title

      Psychiatry Investigation

      Volume: 16 Issue: 3 Pages: 220-233

    • DOI

      10.30773/pi.2019.01.16

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant Cerebellar-Cerebral Functional Connectivity in Children and Adolescents with Autism Spectrum Disorder2018

    • Author(s)
      Ryuzo Hanaie, Ikuko Mohri, Kuriko Kagitani-Shimono, Masaya Tachibana, Junko Matsuzaki, Ikuko Hirata, Fumiyo Nagatani, Yoshiyuki Watanabe, Taiichi Katayama, Masako Taniike
    • Journal Title

      Frontiers in Human Neuroscience

      Volume: 12 Pages: 1-13

    • DOI

      10.3389/fnhum.2018.00454

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Atypical auditory language processing in adolescents with autism spectrum disorder.2018

    • Author(s)
      Tanigawa J, Kagitani-Shimono K, Matsuzaki J, Ogawa R, Hanaie R, Yamamoto T, Tominaga K, Nabatame S, Mohri I, Taniike M, Ozono K.
    • Journal Title

      Clin Neurophysiol.

      Volume: 18 Issue: 9 Pages: 31098-31098

    • DOI

      10.1016/j.clinph.2018.05.014

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prevalence of antibodies against Borna disease virus proteins in Japanese children with autism spectrum disorder.2018

    • Author(s)
      Honda T, Sofuku K, Matsunaga H, Tachibana M, Mohri I, Taniike M, Tomonaga K.
    • Journal Title

      Microbiol Immunol.

      Volume: ‐ Issue: 7 Pages: 473-476

    • DOI

      10.1111/1348-0421.12603

    • NAID

      40021602292

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Japanese Sleep Questionnaire for Elementary Schoolers (JSQ-ES): validation and population-based score distribution.2018

    • Author(s)
      Kuwada A, Mohri I, Asano R, Matsuzawa S, Kato-Nishimura K, Hirata I, Mitsuhosi T, Kagitani-Shimono K, Nakanishi M, Tachibana M, Ohno Y, Taniike M.
    • Journal Title

      Sleep Medicine

      Volume: 41 Pages: 69-77

    • DOI

      10.1016/j.sleep.2017.07.025

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Delayed mismatch field latencies in autism spectrum disorder with abnormal auditory sensitivity: a magnetoencephalographic study.2017

    • Author(s)
      Matsuzaki J, Kagitani-Shimono K, Sugata H, Hanaie R, Nagatani F, Yamamoto T, Tachibana M, Tominaga K, Hirata M, Mohri I, and Taniike M.
    • Journal Title

      Front Hum Neurosci.

      Volume: 11 Pages: 446-446

    • DOI

      10.3389/fnhum.2017.00446

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of behavioral change after adenotonsillectomy for obstructive sleep apnea in children with autism spectrum disorder.2017

    • Author(s)
      Murata E, Mohri I, Kato-Nishimura K, Iimura J, Ogawa M, Tachibana M, Taniike M.
    • Journal Title

      Res Dev Disabil

      Volume: 65 Pages: 127-139

    • DOI

      10.1016/j.ridd.2017.04.012

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of Antibodies against Borna Disease Virus Proteins in an Autistic Child and Her Mother2017

    • Author(s)
      Honda T, Sofuku K, Matsunaga H, Tachibana M, Mohri I, Taniike M, Tomonaga K.
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 70 Issue: 5 Pages: 599-599

    • DOI

      10.7883/yoken.JJID.2017.E001

    • NAID

      130006096683

    • ISSN
      1344-6304, 1884-2836
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 中学生対象日本語版 BRIEF 構成概念妥当性の検証と標準化.2017

    • Author(s)
      桃田茉子, 浅野良輔, 永谷文代, 宮川広美, 中西真理子, 安田由華, 柴田真理子, 橋本亮太, 毛利育子, 谷池雅子.
    • Journal Title

      心理学研究

      Volume: 88 Pages: 348-357

    • NAID

      130006179846

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Detection of Antibodies against Borna Disease Virus Proteins in an Autistic Child and Her Mother2017

    • Author(s)
      Honda T, Sofuku K, Matsunaga H, Tachibana M, Mohri I, Taniike M, Tomonaga K.
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 70 Issue: 2 Pages: 225-227

    • DOI

      10.7883/yoken.JJID.2016.277

    • NAID

      130005475420

    • ISSN
      1344-6304, 1884-2836
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] White matter volume in the brainstem and inferior parietal lobule is related to motor performance in children with autism spectrum disorder: A voxel-based morphometry study.2016

    • Author(s)
      Hanaie R, Mohri I, Kagitani-Shimono K, Tachibana M, Matsuzaki J, Hirata I, Nagatani F, Watanabe Y, Fujita N, Taniike M.
    • Journal Title

      Autism Research

      Volume: 印刷中 Issue: 9 Pages: 00-00

    • DOI

      10.1002/aur.1605

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] マウス新生仔へのプロスタグランジンD2受容体DP1作動薬による神経細胞の形態や行動への影響2019

    • Author(s)
      早田 敦子、 奥田 健太, 毛利 育子, 橘 雅弥, 新谷 勇介, 菊池 泰河, 中澤 敬信, 谷池 雅子, 橋本 均
    • Organizer
      日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウス新生仔へのプロスタグランジンD2受容体DP1作動薬による神経細胞の形態や行動への影響2018

    • Author(s)
      早田 敦子, 奥田 健太, 毛利 育子, 橘 雅弥, 新谷 勇介, 菊池 泰河, 中澤 敬信, 谷池 雅子, 橋本 均
    • Organizer
      日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム
    • Related Report
      2018 Research-status Report
  • [Presentation] Aberrant cerebellar-cerebro functional connectivity in children and adolescents with autism spectrum disorder2018

    • Author(s)
      Hanaie R, Mohri I, Kagitani-Shimono K, Tachibana M, Nagatani F, Watanabe Y, Taniike M.
    • Organizer
      INSAR 2018.
    • Related Report
      2018 Research-status Report
  • [Presentation] Clasmatodendrosis is associated with dendritic spines and does not represent autophagic astrocyte death in influenza-associated encephalopathy.2018

    • Author(s)
      Tachibana M, Mohri I, Kagitani-Shimono K, Fushimi H, Inoue T, Kakuta Y, Murayama S, Nakayama M, Ozono K, Taniike M.
    • Organizer
      The International Society of Neuropathology 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] プロスタグランジンD2受容体DP1を介したマウス神経細胞の形態変化の解析2017

    • Author(s)
      奥田健太,早田敦子,毛利育子,新谷勇介,加茂俊彦,中澤敬信,谷池雅子, 橋本均
    • Organizer
      第132回 日本薬理学会 近畿部会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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