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

2019 Fiscal Year Final Research Report

• 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 (高橋葵) 東京女子医科大学, 医学部, 助教 (80760074)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 軸索ガイダンス分子

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.

Free Research Field

神経科学

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。