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Role of paraventricular thalamic nucleus in bipolar disorder

Research Project

Project/Area Number 17H01573
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionJuntendo University (2020-2021)
Institute of Physical and Chemical Research (2017-2019)

Principal Investigator

KATO TADAFUMI  順天堂大学, 医学部, 教授 (30214381)

Co-Investigator(Kenkyū-buntansha) 笠原 和起  国立研究開発法人理化学研究所, 脳神経科学研究センター, 上級研究員 (50344031)
島 康之  国立研究開発法人理化学研究所, 脳神経科学研究センター, 上級研究員 (60815885)
窪田 美恵 (坂下美恵)  順天堂大学, 大学院医学研究科, 特任准教授 (90344035)
Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥40,430,000 (Direct Cost: ¥31,100,000、Indirect Cost: ¥9,330,000)
Fiscal Year 2021: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2020: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2019: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2018: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2017: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Keywords双極性障害 / 視床室傍核 / ミトコンドリア / ミトコンドリアDNA / 神経科学 / 脳神経疾患 / 脳・神経 / ゲノム / バイオテクノロジー
Outline of Final Research Achievements

In bipolar patients and controls, paraventricular thalamic nucleus (PVT) were identified by calretinin staining. Double staining with anti-cytochrome c oxidase (COX) and anti-succinate dehydrogenase (SDH) antibodies was used to identify cells with mitochondrial dysfunction and anti-8-OHdG antibody immunostaining was used to evaluate DNA oxidation. Cells with mitochondrial dysfunction were identified in the PVT. We attempted to create a reporter mouse that expresses Cre specifically in the PVT by dividing Cre into two parts and expressing them as a fusion protein via a 2A sequence downstream of Gbx2 and Maob, and then aggregating them by drug administration. However, Cre activity was not obtained, and adeno-associated viruses were used in subsequent experiments.

Academic Significance and Societal Importance of the Research Achievements

双極性障害において、視床室傍核にミトコンドリア機能障害を持つ細胞が同定されたことは、双極性障害の原因脳部位が視床室傍核である可能性に矛盾しない。今後、この所見の特異性を更に確認すると共に、動物モデルで視床室傍核病変と双極性障害の症状との関連性が確認されれば、双極性障害の病態理解を進めることになる。双極性障害の原因が明らかとなれば、その診断法や新たな治療法の開発にもつながる。現在、双極性障害の初発抑うつエピソードはうつ病と診断され、結果的には適切でない治療を受けざるを得ないが、今後、こうした状況が改善することが期待される。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (19 results)

All 2022 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 11 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (2 results)

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

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of California San Diego/Univ. of South California, Los Angeles/Wake Forest School of Medicine(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] McGill University(カナダ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] マギル大学(カナダ)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Phenethylamine is a substrate of monoamine oxidase B in the paraventricular thalamic nucleus2022

    • Author(s)
      Obata Youhei、Kubota-Sakashita Mie、Kasahara Takaoki、Mizuno Masafumi、Nemoto Takahiro、Kato Tadafumi
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 17-17

    • DOI

      10.1038/s41598-021-03885-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [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] Brain-specific heterozygous loss-of-function of ATP2A2, endoplasmic reticulum Ca<sup>2+</sup>pump responsible for Darier's disease, causes behavioral abnormalities and a hyper-dopaminergic state2021

    • Author(s)
      Nakajima Kazuo、Ishiwata Mizuho、Weitemier Adam Z、Shoji Hirotaka、Monai Hiromu、Miyamoto Hiroyuki、Yamakawa Kazuhiro、Miyakawa Tsuyoshi、McHugh Thomas J、Kato Tadafumi
    • Journal Title

      Human Molecular Genetics

      Volume: 30 Issue: 18 Pages: 1762

    • DOI

      10.1093/hmg/ddab137

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ntrk1 mutation co-segregating with bipolar disorder and inherited kidney disease in a multiplex family causes defects in neuronal growth and depression-like behavior in mice2020

    • Author(s)
      Nakajima Kazuo、Miranda Alannah、Craig David W.、Shekhtman Tatyana、Kmoch Stanislav、Bleyer Anthony、Szelinger Szabolcs、Kato Tadafumi、Kelsoe John R.
    • Journal Title

      Translational Psychiatry

      Volume: 10 Issue: 1 Pages: 407-407

    • DOI

      10.1038/s41398-020-01087-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Unbiased PCR-free spatio-temporal mapping of the mtDNA mutation spectrum reveals brain region-specific responses to replication instability2020

    • Author(s)
      Bagge Emilie Kristine、Fujimori-Tonou Noriko、Kubota-Sakashita Mie、Kasahara Takaoki、Kato Tadafumi
    • Journal Title

      BMC Biology

      Volume: 18 Issue: 1 Pages: 150-150

    • DOI

      10.1186/s12915-020-00890-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [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] 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] Presynaptic dysregulation of the paraventricular thalamic nucleus causes depression-like behavior.2019

    • Author(s)
      Kato TM, Fujimori-Tonou N, Mizukami H, Ozawa K., Fujisawa S, Kato T.
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 16506-16506

    • DOI

      10.1038/s41598-019-52984-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Current understanding of bipolar disorder: Toward integration of biological basis and treatment strategies2019

    • Author(s)
      Kato T
    • Journal Title

      Psychiatry and Clinical Neurosciences

      Volume: 73 Issue: 9 Pages: 526-540

    • DOI

      10.1111/pcn.12852

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ant1 mutant mice bridge the mitochondrial and serotonergic dysfunctions in bipolar disorder2018

    • Author(s)
      Kato TM, Kubota-Sakashita M, Fujimori-Tonou N, Saitow F, Fuke S, Masuda A, Itohara S, Suzuki H, Kato T.
    • Journal Title

      Molecular Psychiatry

      Volume: 23 Issue: 10 Pages: 2039-2049

    • DOI

      10.1038/s41380-018-0074-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] What Can Mitochondrial DNA Analysis Tell Us About Mood Disorders?2018

    • Author(s)
      Kasahara T, Kato T.
    • Journal Title

      Biological Psychiatry

      Volume: 83 Issue: 9 Pages: 731-738

    • DOI

      10.1016/j.biopsych.2017.09.010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 変異Polgトランスジェニックマウスに見られたうつ病様エピソードとそのメカニズム2017

    • Author(s)
      加藤忠史
    • Organizer
      第39回日本生物学的精神医学会・第47回日本神経精神薬理学会(BPNP2017)合同年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] mmunohistochemical analyses of paraventricular thalamic nucleus (PVT) in human postmortem brains.2017

    • Author(s)
      1.Kubota-Sakashita M, Mechawar N, Shimogori T, Turecki G, Kato T
    • Organizer
      Society for Neuroscience (SfN)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 精神疾患動態研究チーム

    • URL

      http://mdmd.riken.jp/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 精神疾患動態研究チーム

    • URL

      http://www.brain.riken.go.jp/labs/mdmd/

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2023-01-30  

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