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Understanding the schizophrenia-related neural circuits based on transposon dynamics

Planned Research

Project AreaConstructive understanding of multi-scale dynamism of neuropsychiatric disorders
Project/Area Number 18H05430
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKumamoto University

Principal Investigator

岩本 和也  熊本大学, 大学院生命科学研究部(医), 教授 (40342753)

Project Period (FY) 2018-06-29 – 2023-03-31
Project Status Granted (Fiscal Year 2022)
Budget Amount *help
¥94,120,000 (Direct Cost: ¥72,400,000、Indirect Cost: ¥21,720,000)
Fiscal Year 2022: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2021: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2020: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2019: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2018: ¥21,320,000 (Direct Cost: ¥16,400,000、Indirect Cost: ¥4,920,000)
Keywords体細胞変異 / トランスポゾン / 次世代シークエンス / 統合失調症 / 母体免疫活性化 / エピジェネティクス / 精神疾患 / 動物モデル
Outline of Annual Research Achievements

主要な精神疾患である統合失調症では、患者死後脳由来神経細胞において、内在性レトロトランスポゾンLINE-1のゲノムコピー数増大が見いだされている。本研究計画では、LINE-1のゲノムコピー数増大の分子機構の解析と、精神疾患病態との関連を、動物モデルを用いて検討を行う。動物モデルとして、母体免疫活性化を対象とし、妊娠マウスへのpoly(I:C)投与モデル、および、インフルエンザウイルス直接感染モデルを用いる。本年度は、本研究計画において新たに構築したLINE-1新規転移をモニターする、LINE1-EGFPマウス、および、プロモーター領域を改変したtrLINE-1-EGFPマウスについて、転移活性の検討を行った。その結果、両系統とも成体脳においてEGFP陽性細胞が検出された。現在、poly(I:C)投与の影響の検討を実施し、次年度に評価を行う。インフルエンザウイルス直接感染モデルにおいては、生後直後の脳試料でのRRBS法による網羅的DNAメチル化解析のデータ解析を継続した。RNA-seq法によるトランスクリプトーム解析では、神経機能に関連する遺伝子群の発現上昇を認めた。これらの遺伝子群の一部ではDNAメチル化状態の変動を伴っていることが示唆されたため、成体でのDNAメチル化および遺伝子発現についてのオミックス解析データの取得を行った。全ての動物実験は、熊本大学動物実験倫理委員会の承認を得、動物実験ガイドラインに従って実験を行った。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

LINE-1転移の分子機構解析が順調に進展している。インフルエンザウイルス直接感染モデルについて、オミックス解析が順調に進展している。

Strategy for Future Research Activity

最終年度では、複数の動物モデルにおけるオミックスデータの解析を終了し、また、転移モニターマウス等を用いることにより、母体免疫活性化とLINE-1転移および精神疾患との関連について一定の結論を得る。

Report

(4 results)
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report

Research Products

(25 results)

All 2021 2020 2019

All Journal Article (17 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 14 results) Presentation (8 results) (of which Invited: 8 results)

  • [Journal Article] Cell-type-specific DNA methylation analysis of the frontal cortices of mutant Polg1 transgenic mice with neuronal accumulation of deleted mitochondrial DNA2021

    • Author(s)
      Sugawara H, Bundo M, Kasahara T, Nakachi Y, Ueda J, Kubota-Sakashita M, Iwamoto K, Kato T
    • Journal Title

      Molecular Brain

      Volume: 15 Issue: 1 Pages: 9-9

    • DOI

      10.1186/s13041-021-00894-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive DNA Methylation Analysis of Human Neuroblastoma Cells Treated With Haloperidol and Risperidone2021

    • Author(s)
      Du Jianbin、Nakachi Yutaka、Kiyono Tomoki、Fujii Shinya、Kasai Kiyoto、Bundo Miki、Iwamoto Kazuya
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 14 Pages: 792874-792874

    • DOI

      10.3389/fnmol.2021.792874

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell type-specific DNA methylation analysis of the prefrontal cortex of patients with schizophrenia2021

    • Author(s)
      Ueda J, Bundo M, Nakachi Y, Kasai K, Kato T, Iwamoto K
    • Journal Title

      Psychiatry and Clinical Neurosciences

      Volume: 75 Issue: 9 Pages: 297-299

    • DOI

      10.1111/pcn.13282

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inter‐breeder differences in prepulse inhibition deficits of C57BL/6J mice in a maternal immune activation model2021

    • Author(s)
      Kobayashi Yutaro、Inaba Hiroyoshi、Iwakura Yuriko、Namba Hisaaki、Sotoyama Hidekazu、Murata Yui、Iwamoto Kazuya、Nawa Hiroyuki
    • Journal Title

      Neuropsychopharmacology Reports

      Volume: 41 Issue: 3 Pages: 416-421

    • DOI

      10.1002/npr2.12178

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decreased DNA methylation at promoters and gene-specific neuronal hypermethylation in the prefrontal cortex of patients with bipolar disorder2021

    • Author(s)
      Bundo M, Ueda J, Nakachi Y, Kasai K, Kato T, Iwamoto K.
    • Journal Title

      Molecular Psychiatry

      Volume: 26 Issue: 7 Pages: 3407-3418

    • DOI

      10.1038/s41380-021-01079-0

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification and functional characterization of the extremely long allele of the serotonin transporter-linked polymorphic region.2021

    • Author(s)
      1.Ikegame T, Hidaka Y, Nakachi Y, Murata Y, Watanabe R, Sugawara H, Asai T, Kiyota E, Saito T, Ikeda M, Sasaki T, Hashimoto M, Ishikawa T, Takebayashi M, Iwata N, Kakiuchi C, Kato T, Kasai K, Bundo M, Iwamoto K
    • Journal Title

      Transl Psychiatry.

      Volume: 11;11(1) Issue: 1 Pages: 119-119

    • DOI

      10.1038/s41398-021-01242-9

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peroxisome proliferator-activated receptor α as a novel therapeutic target for schizophrenia2020

    • Author(s)
      Wada, Maekawa, Ohnishi et al.
    • Journal Title

      EBioMedicine

      Volume: 62 Pages: 103130-103130

    • DOI

      10.1016/j.ebiom.2020.103130

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Use of the Illumina EPIC methylation array for epigenomic research in the crab-eating macaque (Macaca fascicularis)2020

    • Author(s)
      Yutaka Nakachi, Kazuhiro Ishii, Miki Bundo, Tomoyuki Masuda, Kazuya Iwamoto
    • Journal Title

      Neuropsychopharmacology Reports

      Volume: 40 Issue: 4 Pages: 423-426

    • DOI

      10.1002/npr2.12145

    • NAID

      120007132596

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of Quantitative PCR Assays for Active Long Interspersed Nuclear Element-1 Subfamilies in Mice and Applications to the Analysis of Aging-Associated Retrotransposition2020

    • Author(s)
      Kuroki Ryota、Murata Yui、Fuke Satoshi、Nakachi Yutaka、Nakashima Jun、Kujoth Gregory C.、Prolla Tomas A.、Bundo Miki、Kato Tadafumi、Iwamoto Kazuya
    • Journal Title

      Frontiers in Genetics

      Volume: 11 Pages: 519206-519206

    • DOI

      10.3389/fgene.2020.519206

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Promoter Activity-Based Case-Control Association Study on SLC6A4 Highlighting Hypermethylation and Altered Amygdala Volume in Male Patients With Schizophrenia2020

    • Author(s)
      Ikegame T, Bundo M, Okada N, Murata Y, Koike S, Sugawara H, Saito T, Ikeda M, Owada K, Fukunaga M, Yamashita F, Koshiyama D, Natsubori T, Iwashiro N, Asai T, Yoshikawa A, Nishimura F, Kawamura Y, Ishigooka J, Kakiuchi C, Sasaki T, Abe O, Hashimoto R, Iwata N, Yamasue H, Kato T, Kasai K, Iwamoto K
    • Journal Title

      Schizophrenia Bulletin

      Volume: 46 Issue: 6 Pages: 1577-1586

    • DOI

      10.1093/schbul/sbaa075

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 精神疾患患者試料を使用した1細胞研究の現在2020

    • Author(s)
      岩本和也、文東美紀
    • Journal Title

      医学のあゆみ

      Volume: 276 Pages: 1022-1026

    • Related Report
      2020 Annual Research Report
  • [Journal Article] レトロトランスポゾンが引き起こすヒト疾患2020

    • Author(s)
      文東 美紀, 岩本 和也
    • Journal Title

      医学のあゆみ

      Volume: 273 Pages: 1129-1132

    • Related Report
      2020 Annual Research Report
  • [Journal Article] トランスポゾンはアンチエイジングのターゲットになるか?2020

    • Author(s)
      藤飯 愼也, 岩本 和也
    • Journal Title

      アンチ・エイジング医学

      Volume: 16 Pages: 396-398

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Global DNA hypomethylation and its correlation to the betaine level in peripheral blood of patients with schizophrenia2020

    • Author(s)
      Murata Y, Ikegame T, Koike S, Saito T, Ikeda M, Sasaki T, Iwata N, Kasai K, Bundo M, Iwamoto K
    • Journal Title

      Progress in Neuropsychopharmacology & Biological Psychiatry

      Volume: 99 Pages: 109855-109855

    • DOI

      10.1016/j.pnpbp.2019.109855

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Altered expression of microRNA-223 in the plasma of patients with first-episode schizophrenia and its possible relation to neuronal migration-related genes2019

    • Author(s)
      Zhao, Zhilei, Seiichiro Jinde, Shinsuke Koike, Mariko Tada, Yoshihiro Satomura, Akane Yoshikawa, Yukika Nishimura et al.
    • Journal Title

      Translational Psychiatry

      Volume: 9 Issue: 1 Pages: 289-289

    • DOI

      10.1038/s41398-019-0609-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Excess hydrogen sulfide and polysulfides production underlies a schizophrenia pathophysiology.2019

    • Author(s)
      Ide M, et al. .... Kimura H, Yoshikawa T.
    • Journal Title

      EMBO Mol Med.

      Volume: 11(12) Issue: 12

    • DOI

      10.15252/emmm.201910695

    • NAID

      120007132855

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evaluation of the usefulness of saliva for DNA methylation analysis in cohort studies2019

    • Author(s)
      Murata Yui、Fujii Ayaka、Kanata Sho、Fujikawa Shinya、Ikegame Tempei、Nakachi Yutaka、Zhao Zhilei、Jinde Seiichiro、Kasai Kiyoto、Bundo Miki、Iwamoto Kazuya
    • Journal Title

      Neuropsychopharmacology Reports

      Volume: 39 Issue: 4 Pages: 301-305

    • DOI

      10.1002/npr2.12075

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 脳神経系における体細胞変異と精神疾患2021

    • Author(s)
      岩本和也
    • Organizer
      第66回日本人類遺伝学会大会・第28回日本遺伝子診療学会大会合同開催シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 遺伝環境相互作用の観点からの脳ゲノム変異と精神疾患2021

    • Author(s)
      岩本和也
    • Organizer
      第43回生物学的精神医学会・第51回日本神経精神薬理学会合同年会シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] LINE-1と精神神経疾患:転移の分子機構と新規解析技術の開発2021

    • Author(s)
      岩本和也
    • Organizer
      第43回生物学的精神医学会・第51回日本神経精神薬理学会合同年会NP 特別企画シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 脳ゲノム解析による精神疾患の病因病態解明2020

    • Author(s)
      岩本和也
    • Organizer
      第10回 都医学研シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] セロトニントランスポーターのエピゲノム解析による精神疾患と認知症の病態解析2020

    • Author(s)
      岩本和也
    • Organizer
      第39回認知症学会シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 精神疾患におけるエピゲノム解析の現状と課題2020

    • Author(s)
      岩本和也
    • Organizer
      第50回日本神経精神薬理学・第42回日本生物学的精神医学会・第4回日本精神薬学会合同年会シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 転移因子の遺伝学とバイオロジー2020

    • Author(s)
      岩本和也
    • Organizer
      第50回日本神経精神薬理学・第42回日本生物学的精神医学会・第4回日本精神薬学会合同年会シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Genetic and epigenetic variations of neuronal cells and their implications for psychiatric disorders.2019

    • Author(s)
      Iwamoto K, Bundo M, Kato T.
    • Organizer
      第41回日本神経科学会大会
    • Related Report
      2019 Annual Research Report
    • Invited

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Published: 2018-07-20   Modified: 2022-12-28  

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