• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



Mood Disorders and Addiction

開催日 2014/9/12
時間 10:00 - 11:00
会場 Room I(311+312)
Chairperson(s) 尾崎 紀夫 / Norio Ozaki (名古屋大学大学院医学系研究科 / Department of Psychiatry, Nagoya University Graduate School of Medecine, Japan)
尾上 浩隆 / Hirotaka Onoe (独立行政法人理化学研究所ライフサイエンス技術基盤研究センター / RIKEN Center for Life Science Technologies, Japan)

Long-term imipramine treatment up-regulates NMDA receptors by epigenetic mechanisms in mouse cortical cultured neurons

  • O2-I-2-1
  • Nghia Nguyen:1 Takae Hirasawa:1 Hirotake Kasai:2 Chie Obata:1 Kohji Moriishi:2 Kazuki Mochizuki:3 Takeo Kubota:1 
  • 1:Dept. Epigenetics, Univ of Yamanashi, Chuo, Japan 2:Dept. Microbiology, Univ of Yamanashi, Chuo, Japan 3:Faculty of Life and Environmental Sciences, Univ of Yamanashi, Kofu, Japan 

Imipramine, a major antidepressant, is known to inhibit the re-uptake of serotonin and noradrenaline, which is thought to contribute to the recovery from depression. It has recently been reported that imipramine can acutely inhibit NMDA receptor activity. However, it is not known about the long-term effect of imipramine on NMDA receptor. Therefore, we investigated the acute and long-term effects of imipramine on NMDA receptor in primary cortex neurons obtained from mice at embryonic Day 15 (E15) using fluorescence calcium imaging.
As a result, the acute (30 sec) imipramine treatment dose-dependently decreased the intracellular calcium ([Ca2+]i) influx mediated by NMDA receptors. However, the long-term treatment of imipramine (48 hrs) increased [Ca2+]i influx mediated by NMDA receptors. Furthermore, the long-term treatment induced the increase in expression of NR2B protein, one of the subunit of NMDA receptors. To evaluate the mechanism, we investigate the HDAC activity and expression following 48 hr imipramine treatment, the result showed the global HDAC activity, together with HDAC3 and HDAC4 protein expressions, were decreased in imipramine-treated neurons. Moreover, acetyl histone H3K9 and H3K27 expression were increased at both the global level and the local chromatin of NR2B promoter genes following 48 hr-treated imipramine. Taken together, these results suggested that imipramine has two kind of effect, acute and long-term, on NMDA receptors and imipramine directly enhances NR2B expression through epigenetic regulation mediated by HDAC acitivity.

Copyright © Neuroscience2014. All Right Reserved.