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Study of Effect of neonatal hyperbilirubinemia on neuronal development.

Research Project

Project/Area Number 18K07818
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionShiga University of Medical Science

Principal Investigator

MARUO YOSHIHIRO  滋賀医科大学, 医学部, 教授 (80314160)

Co-Investigator(Kenkyū-buntansha) 中原 小百合  滋賀医科大学, 医学部, 特任助教 (30599204)
柳 貴英  滋賀医科大学, 医学部, 助教 (70418755)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords新生児高ビリルビン血症 / ビリルビン脳症 / ヒト化UGT1Aマウス / 新生児黄疸 / 各黄疸 / ビリルビンUDP-グルクロン酸転移酵素 / 核黄疸 / UGT1A1 / 神経発達
Outline of Final Research Achievements

Using humanized UGT1A mouse, which was provided from Prof. Tukey at University of California San Diego in USA, we analyzed effect of neonatal hyperbilirubinemia on neuronal development as collaboration with Prof. Tukey. As only human and a part of monkeys have a phenomenon of neonatal hyperbilirubinemia, there was not a good animal model to analyze histological change by neonatal hyperbilirubinemia. Severe neonatal hyperbilirubinemia caused bilirubin encephalopathy (kernicterus) in many neonatal humanized UGT1A mouse. We observed process of development of bilirubin encephalopathy histologically.

Academic Significance and Societal Importance of the Research Achievements

ヒト化UGT1Aマウスの研究は、新生児高ビリルビン血症が人類の発達にどのように影響を及ぼしてきたかを明らかにできることと、新生児高ビリルビン血症にともなうビリルビン脳症(核黄疸)の発症を予防できる研究となる。特に、新生児黄疸を起こす動物がヒトとサルの一部であり、モデル動物がいなかったため、本研究は新たな知見を提供している。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (30 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (4 results) Journal Article (23 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 22 results,  Open Access: 13 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] University of California San Diego(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] カリフォルニア大学サンディエゴ校(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of California, San Diego(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] University of California San Diego(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Chronological changes of serum exosome in preterm infants: A?prospective study2022

    • Author(s)
      Ohta Motoki、Koshida Shigeki、Jimbo Itsuki、Oda Machi、Inoue Ryo、Tsukahara Takamitsu、Terahara Masaki、Yanagi Takahide、Nakahara Sayuri、Shibata Masami、Tsutsui Hidemi、Yoshida Daisuke、Furukawa Ouki、Maruo Yoshihiro
    • Journal Title

      Pediatrics International

      Volume: 64 Issue: 1

    • DOI

      10.1111/ped.14933

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intestinal UDP-Glucuronosyltransferase 1A1 and Protection against Irinotecan-Induced Toxicity in a Novel UDP-Glucuronosyltransferase 1A1 Tissue-Specific Humanized Mouse Model2021

    • Author(s)
      Mennillo Elvira、Yang Xiaojing、Weber Andre A.、Maruo Yoshihiro、Verreault Melanie、Barbier Olivier、Chen Shujuan、Tukey Robert H.
    • Journal Title

      Drug Metabolism and Disposition

      Volume: 50 Issue: 1 Pages: 33-42

    • DOI

      10.1124/dmd.121.000644

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Magnetic Resonance Imaging Findings in Preterm Infants With Bilirubin Encephalopathy Beyond Three Years Corrected Age.2021

    • Author(s)
      Okumura A, Kitai Y, Arai H, Hayakawa M, Maruo Y, Kusaka T, Kunikata T, Kumada S, Morioka I.
    • Journal Title

      Pediatr Neurol.

      Volume: 121 Pages: 56-58

    • DOI

      10.1016/j.pediatrneurol.2021.05.019

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neonatal Jaundice in Preterm Infants with Bilirubin Encephalopathy2021

    • Author(s)
      Okumura Akihisa、Ichimura Shintaro、Hayakawa Masahiro、Arai Hiroshi、Maruo Yoshihiro、Kusaka Takashi、Kunikata Tetsuya、Kumada Satoko、Morioka Ichiro
    • Journal Title

      Neonatology

      Volume: 19 Issue: 3 Pages: 1-9

    • DOI

      10.1159/000513785

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ketogenic diet for refractory epilepsy with MEHMO syndrome: Caution for acute necrotizing pancreatitis2021

    • Author(s)
      Mori Mioko、Kumada Tomohiro、Inoue Kenji、Nozaki Fumihito、Matsui Katsuyuki、Maruo Yoshihiro、Yamada Mamiko、Suzuki Hisato、Kosaki Kenjiro、Shibata Minoru
    • Journal Title

      Brain and Development

      Volume: 43 Issue: 6 Pages: 724-728

    • DOI

      10.1016/j.braindev.2021.02.002

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gm14230 controls Tbc1d24-cytoophidia and neuronal cellular juvenescence2021

    • Author(s)
      Morimune T, Tano A, Tanaka Y, Yukiue H, Yamamoto T, Maruo Y, Nishimura M, Tooyama I, Mori M
    • Journal Title

      PLoS ONE

      Volume: 16 Issue: 4 Pages: 1-14

    • DOI

      10.1371/journal.pone.0248517

    • NAID

      120007034814

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Systemic adverse events after screening of retinopathy of prematurity with mydriatic2021

    • Author(s)
      Obata Shumpei、Imamura Taku、Kakinoki Masashi、Yanagi Takahide、Maruo Yoshihiro、Ohji Masahito
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 9 Pages: e0256878-e0256878

    • DOI

      10.1371/journal.pone.0256878

    • NAID

      120007150320

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of intravitreal bevacizumab for retinopathy of prematurity on weight gain2021

    • Author(s)
      Obata Shumpei、Ichiyama Yusuke、Matsumoto Riko、Kakinoki Masashi、Saishin Yoshitsugu、Yanagi Takahide、Maruo Yoshihiro、Ohji Masahito
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 12 Pages: e0261095-e0261095

    • DOI

      10.1371/journal.pone.0261095

    • NAID

      120007180661

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Auditory brainstem response in preterm infants with bilirubin encephalopathy2021

    • Author(s)
      Okumura Akihisa、Kitai Yukihiro、Arai Hiroshi、Hayakawa Masahiro、Maruo Yoshihiro、Kusaka Takashi、Kunikata Tetsuya、Kumada Satoko、Morioka Ichiro
    • Journal Title

      Early Human Development

      Volume: 154 Pages: 105319-105319

    • DOI

      10.1016/j.earlhumdev.2021.105319

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Atypical Familial Mediterranean Fever in a Japanese Boy with Heterozygous MEFV p.Ser503Cys Exon 5 Variant2021

    • Author(s)
      Sato Tomonobu、Takezaki Shunichiro、Goto Takeru、Ishikawa Shinichi、Oura Kazumi、Takahata Asuka、Shiraishi Haruki、Maruo Yuji、Sato Norio、Suganuma Takashi、Mikawa Makoto
    • Journal Title

      Case Reports in Pediatrics

      Volume: 2021 Pages: 1-6

    • DOI

      10.1155/2021/6650226

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fasting-associated urticaria and/or anaphylaxis: A case report2021

    • Author(s)
      Kunitsu Tomoaki、Ueba Satoko、Nakajima Ryo、Nonomura Kazuo、Maruo Yoshihiro、Hide Michihiro
    • Journal Title

      Allergology International

      Volume: 70 Issue: 2 Pages: 271-273

    • DOI

      10.1016/j.alit.2020.09.006

    • NAID

      130008024403

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A nationwide survey of bilirubin encephalopathy in preterm infants in Japan2020

    • Author(s)
      Okumura Akihisa、Morioka Ichiro、Arai Hiroshi、Hayakawa Masahiro、Maruo Yoshihiro、Kusaka Takashi、Kunikata Tetsuya、Kumada Satoko
    • Journal Title

      Brain and Development

      Volume: 42 Issue: 10 Pages: 730-737

    • DOI

      10.1016/j.braindev.2020.06.010

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rotor Syndrome: Glucuronidated Bile Acidemia From Defective Reuptake by Hepatocytes2020

    • Author(s)
      Kimura Akihiko、Kagawa Tatehiro、Takei Hajime、Maruo Yoshihiro、Sakugawa Hiroshi、Sasaki Takahiro、Murai Tsuyoshi、Naritaka Nakayuki、Takikawa Hajime、Nittono Hiroshi
    • Journal Title

      Hepatology Communications

      Volume: 5 Issue: 4 Pages: 629

    • DOI

      10.1002/hep4.1660

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Learning disability and myoclonic epilepsy associated with apparently synonymous but splice‐disrupting JMJD1C variant that led to 21?bp deletion of the transcript2020

    • Author(s)
      Yamada Mamiko、Sokoda Tatsuyuki、Uehara Tomoko、Suzuki Hisato、Takenouchi Toshiki、Yagihashi Tatsuhiko、Maruo Yoshihiro、Kosaki Kenjiro
    • Journal Title

      American Journal of Medical Genetics Part A

      Volume: 182 Issue: 12 Pages: 3064-3067

    • DOI

      10.1002/ajmg.a.61892

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Histamine depolarizes rat intracardiac ganglion neurons through the activation of TRPC non-selective cation channels.2020

    • Author(s)
      Aya Sato, Shiho Arichi, Fumiaki Kojima, Toru Hayashi, Tatsuko Ohba, Dennis Lawrence Cheung, Kei Eto, Madoka Narushima, Hideji Murakoshi, Yoshihiro Maruo, Yuichi Kadoya, Junichi Nabekura, Hitoshi Ishibashi.
    • Journal Title

      Eur J Pharmacol.

      Volume: 886 Pages: 173536-173536

    • DOI

      10.1016/j.ejphar.2020.173536

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Citrullinated fibrinogen is a target of auto-antibodies in interstitial lung disease in mice with collagen-induced arthritis2020

    • Author(s)
      Sato Tomomi、Satooka Hiroki、Ichioka Satoko、Maruo Yoshihiro、Hirata Takako
    • Journal Title

      International Immunology

      Volume: - Issue: 8 Pages: 533-545

    • DOI

      10.1093/intimm/dxaa021

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 母乳性黄疸と体質性黄疸2019

    • Author(s)
      丸尾良浩
    • Journal Title

      周産期医学

      Volume: 49 Pages: 217-221

    • Related Report
      2019 Research-status Report
  • [Journal Article] Pregnancy outcome of Japanese patients with glucokinase?maturity‐onset diabetes of the young2019

    • Author(s)
      Hosokawa Yuki、Higuchi Shinji、Kawakita Rie、Hata Ikue、Urakami Tatsuhiko、Isojima Tsuyoshi、Takasawa Kei、Matsubara Yohei、Mizuno Haruo、Maruo Yoshihiro、Matsui Katsuyuki、Aizu Katsuya、Jinno Kazuhiko、Araki Shunsuke、Fujisawa Yasuko、Osugi Koji、Tono Chikako、Takeshima Yasuhiro、Yorifuji Tohru
    • Journal Title

      Journal of Diabetes Investigation

      Volume: N/A Issue: 6 Pages: 1586-1589

    • DOI

      10.1111/jdi.13046

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The juvenility-associated long noncoding RNA Gm14230 maintains cellular juvenescence2019

    • Author(s)
      Tano Ayami、Kadota Yosuke、Morimune Takao、Jam Faidruz Azura、Yukiue Haruka、Bellier Jean-Pierre、Sokoda Tatsuyuki、Maruo Yoshihiro、Tooyama Ikuo、Mori Masaki
    • Journal Title

      Journal of Cell Science

      Volume: 132 Issue: 8 Pages: 227801-227801

    • DOI

      10.1242/jcs.227801

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] X-linked Charcot-Marie-Tooth disease type 5 with recurrent weakness after febrile illness.2019

    • Author(s)
      Nishikura N, Yamagata T, Morimune T, Matsui J, Sokoda T, Sawai C, Sakaue Y, Higuchi Y, Hashiguchi A, Takashima H, Takeuchi Y, Maruo Y.
    • Journal Title

      Brain Dev

      Volume: 41 Issue: 2 Pages: 201-204

    • DOI

      10.1016/j.braindev.2018.08.006

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hematopoietic Stem Cell Transplantation for Progressive Combined Immunodeficiency and Lymphoproliferation in Activated PI3K <delta> Syndrome Type 12018

    • Author(s)
      Okano T, Imai K, ..., Nonoyama S, Morio T. et al.
    • Journal Title

      J Allergy Clin Immunol

      Volume: 印刷中 Issue: 1 Pages: 266-275

    • DOI

      10.1016/j.jaci.2018.04.032

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Postnatal developmental changes in the sensitivity of L-type Ca2+ channel to inhibition by verapamil in a mouse heart model.2018

    • Author(s)
      Sagawa H, Hoshino S, Yoshioka K, Ding WG, Omatsu-Kanbe M, Nakagawa M, Maruo Y, Matsuura H.
    • Journal Title

      Pediatr Res

      Volume: 83 Pages: 1207-1217

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The histological findings in transposition of the great artery with severe persistent pulmonary hypertension of the newborn2018

    • Author(s)
      Hoshino Shinsuke、Somura Junpei、Furukawa Ouki、Yanagi Takahide、Maruo Yoshihiro
    • Journal Title

      Journal of Cardiology Cases

      Volume: 17 Issue: 5 Pages: 159-162

    • DOI

      10.1016/j.jccase.2018.01.003

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Tissue‐specific Humanized Models Expressing Human UGT1A12020

    • Author(s)
      Mennillo E, Yang X, Weber A, Chen S, MaruoY, Tukey RH.
    • Organizer
      Experimental Biology 2020 Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] ビリルビンUDP-グルクロン酸転移酵素と新生児黄疸2018

    • Author(s)
      丸尾良浩
    • Organizer
      第5回大阪小児科医会総会・教育セミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Remarks] UCSD Superfund Research Center

    • URL

      http://superfund.ucsd.edu

    • Related Report
      2021 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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