The role of long-term memory formation in axon guidance molecules

• Project/Area Number: 17K14964
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo Women's Medical University (2018-2019); Yokohama City University (2017)
• Principal Investigator: Jitsuki Aoi 東京女子医科大学, 医学部, 助教 (80760074)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 軸索ガイダンス分子 / セマフォリン / AMPA型受容体 / 軸索ガイダンス / シナプス可塑性

Outline of Final Research Achievements

The formation of long-term memory requires gene expression and new protein synthesis. However, it is not clear what kind of molecule regulate the long-term memory. We have previously reported that the secretory axon guidance molecule semaphorin 3A (Sema3A) drives synaptic delivery of AMPA-type glutamate receptors (AMPARs), which is the molecular basis of memory formation, is required for establishment of short-term memory. In the present study, we examined whether Sema3A facilitates de novo synthesis of AMPARs, and regulates the formation of long-term memory. By clarifying the role of Sema3A in long-term memory formation, it is expected the development of drug discovery targeting Sema3A and elucidation of the pathophysiology of mental disorders associated with memory impairment.

Academic Significance and Societal Importance of the Research Achievements

Sema3Aはそのシグナル分子は脳・神経疾患との関与が報告されており、実際、アルツハイマー型認知症患者の死後脳において、Sema3A の発現が増加するとの報告がある（内田ら., Gene Cells 2005; Goodら., J Neurochem 2004）。従って、記憶形成の障害による疾患のメカニズムを解明するためにも長期記憶形成時のSema3A の生体内における分泌動態とそのメカニズムを明らかにすることは重要である。本研究で得られる知見は、Sema3A をターゲットとしたアルツハイマー病をはじめとする脳・神経疾患の治療法の開発につながると期待される。

Research Products

• [Journal Article] Network-guided analysis of hippocampal proteome identifies novel proteins that colocalize with Aβ in a mice model of early-stage Alzheimer’s disease (2019)
  • Author(s): Aladeokin Aderemi Caleb、Akiyama Tomoko、Kimura Ayuko、Kimura Yayoi、Takahashi-Jitsuki Aoi、Nakamura Haruko、Makihara Hiroko、Masukawa Daiki、Nakabayashi Jun、Hirano Hisashi、Nakamura Fumio、Saito Takashi、Saido Takaomi、Goshima Yoshio
  • Journal Title: Neurobiology of Disease Volume: 132 Pages: 104603-104603
  • DOI: 10.1016/j.nbd.2019.104603
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Proteome and behavioral alterations in phosphorylation-deficient mutant Collapsin Response Mediator Protein2 knock-in mice. (2018)
  • Author(s): Nakamura H, Jitsuki-Takahashi A, Makihara H, Asano T, Kimura Y, Nakabayashi J, Yamashita N, Kawamoto Y, Nakamura F, Ohshima T, Hirano H, Tanaka F, Goshima Y
  • Journal Title: Neurochemistry international Volume: 119 Pages: 207-217
  • DOI: 10.1016/j.neuint.2018.04.009
  • Peer Reviewed
• [Journal Article] CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage (2018)
  • Author(s): Abe Hiroki、Jitsuki Susumu、Nakajima Waki、Murata Yumi、Jitsuki-Takahashi Aoi、Katsuno Yuki、Tada Hirobumi、Sano Akane、Suyama Kumiko、Mochizuki Nobuyuki、Komori Takashi、Masuyama Hitoshi、Okuda Tomohiro、Goshima Yoshio、Higo Noriyuki、Takahashi Takuya
  • Journal Title: Science Volume: 360 Issue: 6384 Pages: 50-57
  • DOI: 10.1126/science.aao2300
  • Peer Reviewed / Open Access
• [Presentation] Phosphorylation of Collapsin Response Mediator Protein 1 by Semaphorin 3A-Fyn signaling regulates dendritic development (2019)
  • Author(s): A Jitsuki-Takahashi, T Kawashima, S Jitsuki, T Takahashi, Y Goshima, F Nakamura
  • Organizer: NEURO2019
  • Int'l Joint Research