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Reexamination of adult neurogenesis in the marmoset and human hippocampus

Research Project

Project/Area Number 19K06930
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46020:Anatomy and histopathology of nervous system-related
Research InstitutionJuntendo University (2021-2022)
Tokyo Medical University (2019-2020)

Principal Investigator

Seki Tatsunori  順天堂大学, 医学部, 非常勤講師 (20175417)

Co-Investigator(Kenkyū-buntansha) 柏木 太一  東京医科大学, 医学部, 助教 (10398232)
篠原 広志  東京医科大学, 医学部, 講師 (10455793)
權田 裕子  東京医科大学, 医学部, 講師 (60424181)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords成体脳ニューロン新生 / 海馬 / ヒト / マーモセット / 未熟ニューロン / 可塑性 / 顆粒細胞 / 新生ニューロン / 未熟ニューロンマーカー / PSA-NCAM / DCX
Outline of Research at the Start

脳の大部分では、成体になるとニューロンは新生しないが、海馬の顆粒細胞層では成体になってもニューロンの新生が続いている。この「成体脳のニューロン新生」は、現在再生医療、記憶・学習機構、精神疾患など様々な分野で精力的に研究されている。このような研究は主にネズミで行われていたが、成人の海馬でどの程度ニューロンが新生されているのかについては矛盾した結果の報告が多数あり未だに結論が出ていない。本研究の目的は、この問題の決着を目指して、成人とヒトに近いサル(マーモセット)を用いて、ヒトのニューロン新生について再検討することである。

Outline of Final Research Achievements

Studies in rodents have demonstrated that adult neurogenesis occurs in the granule cell layer (GCL) of the hippocampus, and is involved in various hippocampal functions, such as memory and learning, and pathological conditions. However, it remains controversial as to what extent adult neurogenesis actually occurs in the adult human hippocampus. To address this question, we analyzed immature neuronal marker-positive (INM+) cells and proliferating neuronal progenitor cells in humans and marmosets. The present study shows that marmosets and humans harbor abundant INM+ cells not only in the GCL, but also in the hilus, unlike rodents. Although in marmosets, newly generated neurons were always detected in the GCL, but in humans, there were few proliferating neuronal progenitors. These results suggest that the INM+ cells in the adult human hippocampus are not newly generated neurons, and may compensate for the decline in plasticity by a low level of neurogenesis.

Academic Significance and Societal Importance of the Research Achievements

本研究は、ヒトの海馬のニューロン新生は低いが、未熟な性質のニューロンは豊富に存在することを示している。この未熟な性質のニューロンは、海馬の可塑性(記憶・学習の基盤)や神経再生に関与している可能性があり、学術的にも社会的にも意義があると考えている。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (21 results)

All 2023 2021 2020 2019 Other

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (10 results) (of which Invited: 4 results) Remarks (3 results)

  • [Journal Article] The PSA-NCAM-positive "immature" neurons: An old discovery providing new vistas on brain structural plasticity2021

    • Author(s)
      Luca Bonfanti, Tatsunori Seki
    • Journal Title

      Cells

      Volume: 10 Issue: 10 Pages: 2542-2542

    • DOI

      10.3390/cells10102542

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The long-term prognosis of hippocampal neurogenesis and behavioral changes of offspring from rats exposed to valproic acid during pregnancy2021

    • Author(s)
      Masanobu Ito, Tomoya Kinjo, Tatsunori Seki, Junko Horie, Toshihito Suzuki
    • Journal Title

      Neuropsychopharmacol Rep

      Volume: 41 Issue: 2 Pages: 260-264

    • DOI

      10.1002/npr2.12181

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 成人海馬のニューロン新生: 研究は一周して出発点に戻る2021

    • Author(s)
      石龍徳
    • Journal Title

      東京医科大学雑誌

      Volume: 79 Pages: 197-207

    • NAID

      120007164175

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Understanding the Real State of Human Adult Hippocampal Neurogenesis From Studies of Rodents and Non-human Primates2020

    • Author(s)
      Seki Tatsunori
    • Journal Title

      Frontiers in Neuroscience

      Volume: 14 Pages: 839-839

    • DOI

      10.3389/fnins.2020.00839

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 海馬の顆粒細胞の発生-その発生は胎生~成体期まで続く2020

    • Author(s)
      石龍徳
    • Journal Title

      Clinical Neuroscience

      Volume: 38 Pages: 1523-1525

    • Related Report
      2020 Research-status Report
  • [Journal Article] The polarity and properties of radial glia-like neural stem cells are altered by seizures with status epilepticus: Study using an improved mouse pilocarpine model of epilepsy2020

    • Author(s)
      Sasaki-Takahashi N, Shinohara H, Shioda S, Seki T.
    • Journal Title

      Hippocampus

      Volume: 30 Issue: 3 Pages: 250-262

    • DOI

      10.1002/hipo.23153

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Non-radial tortuous migration with cell polarity alterations of newly generated granule neurons in the neonatal rat dentate gyrus2019

    • Author(s)
      Namba T, Shinohara H, Seki T
    • Journal Title

      Brain Struct Funct

      Volume: 224 Issue: 9 Pages: 3247-3262

    • DOI

      10.1007/s00429-019-01971-0

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Analysis of proliferating neuronal progenitors and immature neurons in the human hippocampus surgically removed from control and epileptic patients.2019

    • Author(s)
      Seki T, Hori T, Miyata H, Maehara M, Namba T
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 18194-18194

    • DOI

      10.1038/s41598-019-54684-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 海馬歯状回は様式や性質が異なる神経前駆細胞により形成される2023

    • Author(s)
      篠原 広志、 石 龍徳、 高橋 宗春
    • Organizer
      第128回日本解剖学会総会・全国学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] てんかん患者とてんかんモデル動物における成体海馬ニューロン新生2021

    • Author(s)
      石龍徳
    • Organizer
      第54回てんかん学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] ヒト海馬の成体脳ニューロン新生2021

    • Author(s)
      石龍徳
    • Organizer
      第126回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 海馬歯状回顆粒細胞は2つの異なる経路を移動する前駆細胞によって形成される2021

    • Author(s)
      篠原 広志, 石 龍徳
    • Organizer
      第126回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 発生期海馬における神経幹細胞の特性に関与する因子の発現解析2021

    • Author(s)
      柏木 太一, 塩田 清二, 石 龍徳
    • Organizer
      第126回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Adult hippocampal neurogenesis and immature neuronal marker-expressing neurons2021

    • Author(s)
      Tatsunori Seki
    • Organizer
      The 17th Adult-neurogenesis conference in Japan
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] ヒトの海馬ではどの程度成体脳ニューロン新生が起こっているのか?2020

    • Author(s)
      石龍徳
    • Organizer
      第43回日本神経科学学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 背側および腹側の異なる経路によって海馬歯状回顆粒細胞層は形成される2020

    • Author(s)
      篠原 広志, 石 龍徳
    • Organizer
      第43回日本神経科学学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Analysis of cellular migration in developmental dentate gyrus2019

    • Author(s)
      Shinohara H, Seki T
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト海馬のニューロン新生;その進化学的考察2019

    • Author(s)
      石龍徳
    • Organizer
      海馬と高次脳機能学会
    • Related Report
      2019 Research-status Report
  • [Remarks] 石龍徳の研究ページ

    • URL

      https://sekitatsulab.jimdofree.com

    • Related Report
      2022 Annual Research Report
  • [Remarks] 石 龍徳の研究ページ

    • URL

      https://sekitatsulab.jimdofree.com

    • Related Report
      2021 Research-status Report
  • [Remarks] 東京医科大学 組織・神経解剖学分野

    • URL

      https://tokyomed-histology-neuroanatomy.jimdofree.com/

    • Related Report
      2020 Research-status Report 2019 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2024-01-30  

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