Screening of molecules responsible for signaling from nucleus to synapses in emotional memory

• Project/Area Number: 26430076
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Toyo University
• Principal Investigator: Kojima Nobuhiko 東洋大学, 生命科学部, 教授 (80215251)
• Co-Investigator(Kenkyū-buntansha): 遠藤 昌吾 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (60192514)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: シナプス可塑性 / 遺伝子発現 / PC12細胞 / 突起伸長 / 樹状突起スパイン / CRE転写調節 / 最初期遺伝子 / cAMP / 神経突起 / 海馬ニューロン / 転写調節因子

Outline of Final Research Achievements

It is well known that CRE transcriptional regulation and structural change in synapses are essential for emotional memory formation. However, the molecular basis is not clear. ICER, which is a CRE transcription repressor, suppresses emotional memory formation in mice. The aim of the study is to identify the ICER target genes and to investigate the involvement of ICER in synaptic structural changes. Using gene expression system, we revealed that ICER promotes the elongation of protrusion in neuronal model cells and the change in dendritic spines of primary cultured neurons. In addition, we were able to identify ICER target gene candidates in ICER-over expressing PC 12 cells. The results of this study are expected to contribute not only to the molecular mechanism of memory formation but also to elucidation of the cause of psychiatric disorders such as dementia and PTSD.

Research Products

• [Journal Article] X Irradiation Induces Acute Cognitive Decline via Transient Synaptic Dysfunction. (2016)
  • Author(s): Puspitasari A, Koganezawa N, Ishizuka Y, Kojima N, Tanaka N, Nakano T, Shirao T.
  • Journal Title: Radiat Research Volume: 185 Issue: 4 Pages: 423-430
  • DOI: 10.1667/rr14236.1
  • Peer Reviewed / 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] Impact of molecular interactions of metabotropic glutamate receptor and drebrin on synaptic structural plasticity in hippocampal neurons. (2016)
  • Author(s): Kakegawa R, Shiraishi K, Kojima N
  • Organizer: 第３9回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-07-20