Analysis of activity-dependent dynamics of NMDA receptors in mice with age-dependent synaptic dysfunction

• Project/Area Number: 15H06078
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Gunma University
• Principal Investigator: Hanamura Kenji 群馬大学, 大学院医学系研究科, 助教 (40361365)
• Co-Investigator(Renkei-kenkyūsha): TAKATSURU YUSUKE 群馬大学, 大学院医学系研究科, 講師 (30446265)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 樹状突起スパイン / 2光子励起レーザー顕微鏡 / ドレブリン / NMDA受容体 / in vivo imaging / 神経活動依存性 / 加齢脳 / シナプス機能異常 / アクチン細胞骨格 / アクチン結合タンパク質

Outline of Final Research Achievements

In vivo imaging by using two-photon laser microscopy under deep anesthesia revealed dendritic spine morphology of pyramidal neurons in the cerebral cortex of transgenic mice expressing GFP under the control of Thy1-promoter. Analysis of heterozygotes of knockout mice deficient in drebrin A-specific exon or all drebrin isoforms tended to show some changes in turnover rate of dendritic spines compared with wild-type mice. The amount of NMDA receptors in synaptosomes were detected by western blotting.

Research Products

• [Journal Article] Progress in applications of iPSC-derived neurons for evaluation of drugs (2017)
  • Author(s): Koganezawa N, Hanamura K, Shirao T.
  • Journal Title: Folia Pharmacologica Japonica Volume: 149 Issue: 3 Pages: 104-109
  • DOI: 10.1254/fpj.149.104
  • NAID: 130005403859
  • ISSN: 0015-5691, 1347-8397
  • Peer Reviewed
• [Journal Article] The role of drebrinin neurons (2017)
  • Author(s): Shirao T, Hanamura K, Koganezawa N, Ishizuka Y, Yamazaki H, Sekino Y.
  • Journal Title: J. Neurochem. Volume: - Issue: 6 Pages: 819-834
  • DOI: 10.1111/jnc.13988
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The role of drebrin in dendritic spines (2017)
  • Author(s): Koganezawa N, Hanamura K, Sekino Y, Shirao T
  • Journal Title: Mol. Cell. Neurosci. Volume: - Pages: 85-92
  • DOI: 10.1016/j.mcn.2017.01.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Allopregnanolone increases mature excitatory synapses along dendrites via protein kinase A signaling (2015)
  • Author(s): Shimizu H, Ishizuka Y, Yamazaki H, Shirao T.
  • Journal Title: Neuroscience Volume: 305 Pages: 139-145
  • DOI: 10.1016/j.neuroscience.2016.03.015
  • Peer Reviewed
• [Presentation] シナプスイメージングに基づき医薬品の認知機能影響リスクを予測する in vitro 評価系確立の試み (2017)
  • Author(s): 清水英雄、小針彩奈、須知由未子、関口敬洋、花村健次、白尾智明、田辺光男、関野祐子、佐藤薫
  • Organizer: 第59回日本神経化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2017-09-08
• [Presentation] 培養神経細胞を用いたハイコンテントイメージングによるシナプスの解析 (2017)
  • Author(s): 岡丈朗、花村健次、白尾智明
  • Organizer: 第９０回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-15
• [Presentation] ベンゾジアゼピン系薬剤の培養海馬神経細胞シナプス数に対する作用―医薬品の中枢神経系有害反応予測のための新規 in vitro 評価系確立の試み (2017)
  • Author(s): 清水英雄、小針彩奈、須知由未子、関口敬洋、花村健次、白尾智明、田辺光男、関野祐子、佐藤薫
  • Organizer: 第９０回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-15
• [Presentation] Stable fraction of drebrin in dendritic spines is regulated by the isoform conversion (2017)
  • Author(s): Kenji Hanamura, Tomoaki Shirao.
  • Organizer: The 7th International Society of Radiation Neurobiology Conference
  • Place of Presentation: 湯沢（新潟）
  • Year and Date: 2017-02-09
  • Int'l Joint Research
• [Presentation] High-content imaging analysis of glutamatergic synapses using primary cultured neurons (2017)
  • Author(s): Takero Oka, Kenji Hanamura, Noriko Koganezawa, Kazumi Kamiyama, Natsume Tanaka, Tomoaki Shirao
  • Organizer: The 7th International Society of Radiation Neurobiology Conference
  • Place of Presentation: 湯沢（新潟）
  • Year and Date: 2017-02-09
  • Int'l Joint Research
• [Presentation] Quantitative imaging analysis of amyloid beta toxicity using cultured neurons. (2016)
  • Author(s): Tomoaki Shirao, Yuta Ishizuka, Kenji Hanamura, Yasunari Kanda and Yuko Sekino,
  • Organizer: The 5th Annual Meeting of the American Society for Cellular and Computational Toxicology (ASCCT)
  • Place of Presentation: Durham, NC, USA
  • Year and Date: 2016-09-29
  • Int'l Joint Research
• [Presentation] スパイン内のドレブリンの安定性は発達期のアイソフォーム変換によりアクチン細胞骨格依存的に増加する (2016)
  • Author(s): 花村健次、白尾 智明
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-20
• [Presentation] 発達期樹状突起スパインのアクチン細胞骨格成熟とその加齢依存的なシナプス可塑性における役割 (2016)
  • Author(s): 花村健次、児島伸彦、安田浩樹、山﨑博幸、白尾智明
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター（札幌）
  • Year and Date: 2016-03-22
• [Presentation] EphB Extracellular Phosphorylation Controls Pathological Pain and Synaptic Function of NMDA Receptors (2015)
  • Author(s): Hanamura K., Sheffler-Collins S.I., Xia N., Washburn H.R., Tillu D., Hassler S, Spellman D.S., Zhang G., Neubert T.A., Price T.J., Dalva M.B.
  • Organizer: 第58回日本神経化学会大会
  • Place of Presentation: 大宮ソニックシティ（さいたま）
  • Year and Date: 2015-09-11
• [Book] ｉＰＳ細胞の安全・高品質な作製技術 (2016)
  • Author(s): 花村健次、白尾智明
  • Total Pages: 494
  • Publisher: 技術情報協会
• [Remarks] 群馬大学大学院医学系研究科神経薬理学分野
  • URL: http://neuro.dept.med.gunma-u.ac.jp/