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Analysis of Alzheimer's disease model neurons focusing on synaptic dysfunction

Research Project

Project/Area Number 19K08010
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionGunma University

Principal Investigator

Koganezawa Noriko  群馬大学, 大学院医学系研究科, 助教 (90643114)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords樹状突起スパイン / ドレブリン / ハイスループット解析 / 超解像顕微鏡 / シナプス
Outline of Research at the Start

現代の高齢化社会においてアルツハイマー病は原因究明と診断・治療法の開発が待たれている神経変性疾患の一つであるが、細胞死を伴わないシナプス機能不全が認知機能障害と相関することが明らかになっている。シナプス機能にはシナプス後部を構成する樹状突起スパインが重要な役割を果たし、その形態維持にはアクチン線維に結合するドレブリンが関わる。アルツハイマー病の初期症状である記憶障害の基盤にはドレブリンが減少することによるスパイン形態安定性の欠損が考えられる。本研究では病態モデル神経細胞を開発し樹状突起スパイン内のドレブリン等タンパク質の局在性変化に着目したアルツハイマー病のシナプス機能不全の実態解明を目指す。

Outline of Final Research Achievements

Alzheimer’s disease causes cognitive dysfunction such as dementia, and it is reported that the degree of cognitive dysfunction correlates with synaptic dysfunction. It is important to reveal the synaptic dysfunction in Alzheimer’s disease focusing on dendritic spines, because they are the main structures of excitatory synapses. To study Alzheimer’s disease focusing on dendritic spines, a new animal model of Alzheimer’s disease was made in this study. In addition, as an in vitro analysis system is necessary to study the dendritic spine level of the disease, in vitro high-content imaging analysis system was established. Drebrin, an actin-binding protein that accumulates at dendritic spines, is a good marker for synaptic states. The dendritic spines of cultured neurons from a new animal model of Alzheimer’s disease were analyzed focusing on drebrin. It is suggested that the exodus of drebrin from dendritic spines causes synaptic dysfunction.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病脳のシナプス機能不全の実態はその検証があまり進んでいない。本研究ではモデル神経細胞を用いてin vitro解析系を開発し、スパインレベルでの解析を可能とした。今後、さらに検証を進めることでアルツハイマー病におけるシナプス機能不全の実態を明らかにすることができると期待される。さらに本研究では、ドレブリンをシナプス機能マーカーとし、医薬品のシナプス機能安全性評価などへ応用可能なシナプス機能評価のハイスループット化を実現させた。

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

    (24 results)

All 2023 2022 2021 2020 2019

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (18 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Easy and Reproducible Low-Density Primary Culture using Frozen Stock of Embryonic Hippocampal Neurons2023

    • Author(s)
      Koganezawa Noriko、Roppongi Reiko T.、Sekino Yuko、Tsutsui Izuo、Higa Ayaka、Shirao Tomoaki
    • Journal Title

      Journal of Visualized Experiments

      Volume: 191 Issue: 191 Pages: 0-0

    • DOI

      10.3791/64872

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impairment of ciliary dynamics in an APP knock-in mouse model of Alzheimer's disease.2022

    • Author(s)
      Kobayashi Y, Kobuchi S, Koganezawa N, Sekino Y, Shirao T, Saito T, Saido TC, Saito Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 610 Pages: 85-91

    • DOI

      10.1016/j.bbrc.2022.04.050

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NMDA receptor‐dependent and ‐independent effects of natural compounds and crude drugs on synaptic states as revealed by drebrin imaging analysis2021

    • Author(s)
      Koganezawa Noriko、Sekino Yuko、Kawakami Hitomi、Fuchino Hiroyuki、Kawahara Nobuo、Shirao Tomoaki
    • Journal Title

      European Journal of Neuroscience

      Volume: 00 Issue: 11 Pages: 1-13

    • DOI

      10.1111/ejn.15231

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Properties of primary cilia in melanin-concentrating hormone receptor 1-bearing hippocampal neurons in vivo and in vitro.2021

    • Author(s)
      Kobayashi Y, Okada T, Miki D, Koganezawa N, Sekino Y, Shirao T, Dinitz GB, Saito Y.
    • Journal Title

      Neurochem International

      Volume: 142 Pages: 104902-104902

    • DOI

      10.1016/j.neuint.2020.104902

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] High-content imaging analysis for detecting the loss of drebrin clusters along dendrites in cultured hippocampal neurons2019

    • Author(s)
      Hanamura Kenji、Koganezawa Noriko、Kamiyama Kazumi、Tanaka Natsume、Oka Takero、Yamamura Mai、Sekino Yuko、Shirao Tomoaki
    • Journal Title

      Journal of Pharmacological and Toxicological Methods

      Volume: 99 Pages: 106607-106607

    • DOI

      10.1016/j.vascn.2019.106607

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assessment of NMDA receptor inhibition of phencyclidine analogues using a high-throughput drebrin immunocytochemical assay2019

    • Author(s)
      Mitsuoka Toshinari、Hanamura Kenji、Koganezawa Noriko、Kikura-Hanajiri Ruri、Sekino Yuko、Shirao Tomoaki
    • Journal Title

      Journal of Pharmacological and Toxicological Methods

      Volume: 99 Pages: 106583-106583

    • DOI

      10.1016/j.vascn.2019.106583

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Quantitative analysis for drebrin clusters along dendrites using immunocytochemical images of cultured rat hippocampal neurons2023

    • Author(s)
      Shogo Mase, Toshinari Mitsuoka, Noriko Koganezawa, Tomoaki Shirao, Yuko Sekino
    • Organizer
      第12回国際放射線神経生物学会大会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 凍結神経細胞を用いたハイスループットスクリーニング法2023

    • Author(s)
      六本木麗子、小金澤紀子、関野祐子、比嘉彩香、白尾智明
    • Organizer
      第100回日本生理学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ラット海馬培養ニューロンのドレブリン染色画像を用いた発達神経毒性の定量解析2022

    • Author(s)
      間瀬省吾,光岡俊成,小金澤紀子, 山崎博幸, 加藤祐一, 筒井泉雄, 川辺浩志, 白尾智明, 關野祐子
    • Organizer
      第49回日本毒性学会学術年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Proposal of a new AOP for the neurotoxicity and developmental neurotoxicity assessment of glutamate receptor binding agonists that cause learning and memory impairment2022

    • Author(s)
      Shogo Mase, Toshinari Mitsuoka, Hiroyuki Yamazaki, Yonehiro Kanemura, Daiju Yamazaki, Noriko Koganezawa, Yuko Sekino
    • Organizer
      2022 ICCA-LRI and NITE Workshop
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of natural compounds and crude drugs on synaptic states revealed by drebrin imaging analysis2022

    • Author(s)
      Koganezawa N, Sekino Y, Shirao T
    • Organizer
      第11回国際放射線神経生物学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Super-resolved 3D-STED microscopy reveals a layer-specific increase in excitatory synapses in the hippocampal CA1 region of a model mouse of autism spectrum disorder, Neuroligin-3 KO mice2022

    • Author(s)
      Koganezawa N, Hanamura K, Schwark M, Krueger-Burg D, Kawabe H
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 認知症に効く漢方薬スクリーニング:オウバクとオンジの有効可能性2021

    • Author(s)
      小金澤紀子、関野祐子、白尾智明
    • Organizer
      第28回HAB研究機構学術年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Developmental neurotoxicity assessment of glutamate receptor binding agonists that cause learning and memory impairment:analysis of drebrin immunoreactivity in rat hippocampal cultured neuron2021

    • Author(s)
      間瀬省吾, 筒井泉雄, 光岡俊成, 小金澤紀子, 山崎博幸, 加藤祐一, 川辺浩志, 白尾智明, 關野祐子
    • Organizer
      第48回日本毒性学会学術年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Transcriptome analysis of ciliary-dependent GPCR signaling -Identification a novel regulatory step underlying cilia length control2021

    • Author(s)
      Saito Y, Miyamoto T, Sekino Y, Shirao T, Koganezawa N, Kobayashi Y
    • Organizer
      第64回日本神経化学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Effects of a synthetic cannabinoid, CP55940, on synaptogenesis of cultured hippocampal neurons: imaging analysis of drebrin immunocytochemistry2021

    • Author(s)
      間瀬省吾, 光岡俊成, 小金澤紀子, 山崎博幸, 加藤祐一, 筒井泉雄, 川辺浩志, 關野祐子
    • Organizer
      第64回日本神経化学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Assessment of CB agonist CP55940 in maturity for rat hippocampal neurons using a high-throughput immunocytochemical assay and image digital analysis2021

    • Author(s)
      Mitsuoka Toshinari, Mase Syogo, Koganezawa Noriko, Katou Yuuichi, Tsutsui Izuo, Shirao Tomoaki, Sekino Yuko
    • Organizer
      第94回日本薬理学会
    • Related Report
      2020 Research-status Report
  • [Presentation] High-content imaging evaluation of crude drugs effects on synaptic function2020

    • Author(s)
      Koganezawa Noriko、Sekino Yuko、Kawakami Hitomi、Fuchino Hiroyuki、Kawahara Nobuo、Shirao Tomoaki
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Research-status Report
  • [Presentation] NMDA receptor dependent and independent loss of drebrin from dendritic spines induced by crude drugs in Japanese Kampo2020

    • Author(s)
      Koganezawa Noriko、Sekino Yuko、Shirao Tomoaki
    • Organizer
      第63回日本神経化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Loss of drebrin from dendritic spines in hippocampal neurons from Alzheimer’s disease model mouse2020

    • Author(s)
      Noriko Koganezawa, Yuki Kajita, Hiroyuki Yamazakaki, Takashi Saito, Yuko Sekino, Takaomi C Saido and Tomoaki Shirao
    • Organizer
      日本薬理学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Decreased immunoreactivity of drebrin around amyloid plaques in Alzheimer’s diseases model mouse2020

    • Author(s)
      Noriko Koganezawa, Yuki Kajita, Hiroyuki Yamazakaki, Takashi Saito, Yuko Sekino, Takaomi C Saido and Tomoaki Shirao
    • Organizer
      ISRN
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Drebrin depletion affects stability of microtubules in dendrites2019

    • Author(s)
      Koganezawa N., Yamazaki H. and Shirao T.
    • Organizer
      FAOPS2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Drebrin depletion alters NMDAR function and affects stability of microtubule in dendrites2019

    • Author(s)
      Koganezawa N., Yamazaki H. and Shirao T.
    • Organizer
      NEURO2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Alzheimer’s disease model mouse analysis focusing on drebrin2019

    • Author(s)
      Noriko Koganezawa, Yuki Kajita, Hiroyuki Yamazakaki, Takashi Saito, Yuko Sekino, Takaomi C Saido and Tomoaki Shirao
    • Organizer
      SfN2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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

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