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Perspective biological makers for autism spectrum disorders: focus on essential amino acid and its metabolites.

Research Project

Project/Area Number 16K08948
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionKansai Medical University (2019-2020)
Doshisha University (2016-2018)

Principal Investigator

MURAKAMI Yuki  関西医科大学, 医学部, 助教 (50580106)

Project Period (FY) 2016-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords自閉スペクトラム症 / アミノ酸代謝 / 炎症 / トリプトファン / 神経発達症 / キヌレニン / 行動異常 / 母体環境 / 母胎環境 / 脳・神経 / トリプトファン代謝 / 自閉症スペクトラム症
Outline of Final Research Achievements

Autism spectrum disorder (ASD) is one of the most common neurodevelopmental disorders. The diagnosis for ASD is often challenging because these diagnostic approaches are less objective and time consuming. Thus, an appropriate diagnosis needs to consider the applicability of the diagnostic approach. We measured the levels of kynurenine pathway(KP) metabolites in the serum of ASD models mice to assess the potential of KP metabolites as predictive peripheral biomarkers for neurodevelopmental disorders. We found genetical ASD model mice showed drastic changes in KP metabolite concentrations. We also found maternal inflammation dramatically changed KP metabolites in maternal serum, pointing to the ability of kynurenine to cross the placenta and change the KP metabolites which are affected as neuroactive compounds in the fetal brain. Our results suggested that KP metabolites are potential diagnostic biomarkers for neurodevelopmental disorders.

Academic Significance and Societal Importance of the Research Achievements

自閉スペクトラム症(ASD)は神経発達症の一つで、生涯に渡って続く障害である。診断方法は専門的な医師による面接や保護者からの発育状態の聞き取りなど行動観察によるところが大きく、客観的診断マーカーはほとんど明らかにされていない。本研究の成果は、必須アミノ酸という重要な栄養素とその代謝産物がASDの病態に関与している可能性と、それらの測定が診断マーカーとして有用である可能性を示したことである。

Report

(6 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (21 results)

All 2021 2020 2019 2018 2017 2016

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (11 results) (of which Int'l Joint Research: 3 results) Book (2 results)

  • [Journal Article] Decline of Plasma Concentrations of Interleukin-18 in Severely Malnourished Patients with Anorexia Nervosa: Exploratory Analysis.2019

    • Author(s)
      Tanaka S, Oya-Ito T, Murakami Y, Saito K, Furuta S, Yu Y, Imaeda M, Kunimoto S, Ozaki N.
    • Journal Title

      Nutrients.

      Volume: 11(3) Issue: 3 Pages: 1-6

    • DOI

      10.3390/nu11030540

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Information Delivery Methods and their Association with Older Adults Memory and Comprehension.2019

    • Author(s)
      Imamura Y, Murakami Y, Mitani S 他6名
    • Journal Title

      Journal of Aging Science

      Volume: 7(2) Issue: 02 Pages: 1-7

    • DOI

      10.35248/2329-8847.19.07.207

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Altered kynurenine pathway metabolites in a mouse model of human attention-deficit hyperactivity/autism spectrum disorders: A potential new biological diagnostic marker.2019

    • Author(s)
      Murakami Y, Imamura Y, Saito K, Sakai D
    • Journal Title

      Scientific reports

      Volume: 10(1) Issue: 1 Pages: 1-15

    • DOI

      10.1038/s41598-020-60585-3

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Profound haemodynamic response in the prefrontal cortex induced by musical stimuli.2018

    • Author(s)
      Imamura Y, Murakami Y, Miura K, Koh S 他4名
    • Journal Title

      J Neurosci Brain Imaging

      Volume: 2(1:2) Pages: 1-13

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Astroglial major histocompatibility complex class I following immune activation leads to behavioral and neuropathological changes.2018

    • Author(s)
      A Sobue, N Ito, T Nagai, W Shan, K Hada, Nakajima A, Y Murakami, A Mouri, Y Yamamoto, T Nabeshima, K Saito, K Yamada
    • Journal Title

      Glia

      Volume: 66 Issue: 5 Pages: 1034-52

    • DOI

      10.1002/glia.23299

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Kynurenine 3-monooxygenase is implicated in antidepressants-responsive depressive-like behaviors and monoaminergic dysfunctions2017

    • Author(s)
      Tashiro T , Murakami Y , Mouri A , Imamura Y, Nabeshima T, Yamamoto, Y , Saito, K
    • Journal Title

      BEHAVIOURAL BRAIN RESEARCH

      Volume: 317 Pages: 279-285

    • DOI

      10.1016/j.bbr.2016.09.050

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Effect of Histone Acetylation on N-Methyl-D-Aspartate 2B Receptor Subunits and Interleukin-1 Receptors in Association with Nociception-Related Somatosensory Cortex Dysfunction in A Mouse Model of Sepsis2016

    • Author(s)
      Yukio Imamura, Nao Yoshikawa, Yuki Murkami, Satoko Mitani, Naoya Matsumoto,Hisatake Matsumoto, Tomoki Yamada, Kazuma Yamakawa, Junichiro Nakagawa, Hiroshi Ogura, Takeshi Shimazu, Takashi Jin
    • Journal Title

      Shock

      Volume: 45(6) Issue: 6 Pages: 660-667

    • DOI

      10.1097/shk.0000000000000547

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Depressive symptoms as a side effect of Interferon-α therapy induced by induction of indoleamine 2,3-dioxygenase 1.2016

    • Author(s)
      Murakami Y, Ishibashi T, Tomita E, Imamura Y, Tashiro T, Watcharanurak K, Nishikawa M, Takahashi Y, Takakura Y, Mitani S, Fujigaki H, Ohta Y, Kubo H, Mamiya T, Nabeshima T, Kim HC, Yamamoto Y, Saito K.
    • Journal Title

      SCIENTIFIC REPORTS

      Volume: 6 Issue: 1 Pages: 29920-29920

    • DOI

      10.1038/srep29920

    • NAID

      120006323748

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Maternal inflammation is relevant to the risk of neurodevelopmental disorders2021

    • Author(s)
      Yuki Murakmai
    • Organizer
      2021 RIKEN-Luxembourg Digital Scientific Symposium
    • Related Report
      2020 Annual Research Report
  • [Presentation] 妊娠期の母胎炎症によって引き起こされる神経発達障害様モデル2020

    • Author(s)
      村上由希
    • Organizer
      NPBPPP合同年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 注意欠如/多動性障害モデル動物におけるトリプトファン-キヌレニン代謝産物の変化2018

    • Author(s)
      村上由希
    • Organizer
      第22回活性アミンに関するワークショップ
    • Related Report
      2018 Research-status Report
  • [Presentation] A Critical Risk factor for major side effect of interferon-therapy: Stimulated indoleamine 2,3-dioxygenase1 is associated to depressive states.2018

    • Author(s)
      Murakami Y, Imamura Y, Kim HC, Nabeshima T, Saito K.
    • Organizer
      15th International Society for Tryptophan Research (ISTRY) Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Altered Kynurenine Pathway Metabolism in Attention-Deficit/Hyperactivity Disorder model mice: Potential peripheral biomarker for AD/HD.2018

    • Author(s)
      Murakami Y
    • Organizer
      International Symposium「Towards Understanding "INDIVIUALITY"」
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 神経発達障害に関連した遺伝子欠損動物における行動解析とトリプトファン代謝の変化2017

    • Author(s)
      村上由希
    • Organizer
      文部科学省科学研究補助金新学術領域研究 「個性」創発脳 第二回領域会議
    • Related Report
      2017 Research-status Report
  • [Presentation] 薬剤誘発性抑うつ病態におけるトリプトファン代謝の関与2017

    • Author(s)
      村上由希
    • Organizer
      第21回活性アミンに関するワークショップ
    • Related Report
      2017 Research-status Report
  • [Presentation] 妊娠期の母胎炎症によって引き起こされる脳の発達異常とトリプトファン代謝2017

    • Author(s)
      村上由希 酒井大輔
    • Organizer
      第38回日本トリプトファン研究会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] トリプトファン-セロトニン代謝経路に注目したうつ病モデル動物2017

    • Author(s)
      毛利彰宏 渡辺研 國澤和生 勅使河原知明 平川茉実 森優子 藤垣英嗣 村上由希 山本康子 齋藤邦明 鍋島俊隆
    • Organizer
      第38回日本トリプトファン研究会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 神経発達障害に関連した遺伝子欠損動物における行動解析とトリプトファン代謝の変化2016

    • Author(s)
      村上由希
    • Organizer
      第37回日本トリプトファン研究会
    • Place of Presentation
      東京農業大学(東京都世田谷区)
    • Year and Date
      2016-12-10
    • Related Report
      2016 Research-status Report
  • [Presentation] Depressive symptoms, as a side effect of Interferon-alpha therapy induced by induction od indoleamine 2,3-dioxygenase 1.2016

    • Author(s)
      Yuki Murakami, Hyoung-Chun Kim, Toshitaka Nabeshima, Kuniaki Saito他5名
    • Organizer
      30th The International College of Neuropsychopharmacology
    • Place of Presentation
      ソウル(韓国)
    • Year and Date
      2016-07-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Book] Pharmacokinetics and Adverse Effects of Drugs - Mechanisms and Risks Factors. Chapter3 A critical Risk Factor for a Major Side Effect of Interferon-Alpha Therapy: Activated Indoleamine 2,3-dioxygenase 1 is Related to Depressive Symptoms.2018

    • Author(s)
      Murakami Y Imamura Y
    • Total Pages
      20
    • Publisher
      InTech
    • ISBN
      9781789231397
    • Related Report
      2018 Research-status Report
  • [Book] Sepsis. Chapter title: In vivo imaging of septic encephalopathy.2017

    • Author(s)
      Y Imamura, Y Murakami, N Matsumoto, H Matsumoto, S Mitani, K Shimizu, H Ogura, T Shimazu, T Jin
    • Total Pages
      21
    • Publisher
      InTech
    • ISBN
      9789535153610
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2022-01-27  

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