Examination of the interaction of AT2 receptor and neurotransmitter in vascular dementia

2013 Fiscal Year Final Research Report

• Project/Area Number: 24791506
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cerebral neurosurgery
• Research Institution: Ehime University
• Principal Investigator: IWANAMI Jun 愛媛大学, 医学(系)研究科(研究院), 助教 (90624792)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 認知機能 / 血管性認知症 / 糖尿病 / レニン・アンジオテンシン系 / AT2受容体 / NMDA受容体

Research Abstract

Type 2 diabetes mellitus (T2DM) is reported to be associated with increased risk of dementia. We previously reported that stimulation of angiotensin II type 2 (AT2) receptor exerts brain protective effects. Accordingly, we examined the possible synergistic effect of AT2 receptor agonist, C21 and NMDA receptor antagonist, memantine on cognitive impairment in T2DM mice, KKAy. Treatment with C21 or memantine alone at these doses tended to attenuate cognitive function compared with control KKAy without significant difference. Co-administration of C21 and memantine significantly improved cognitive function. C21 treatment increased cerebral blood flow (CBF)and hippocampalfield-excitatory potential (EPSP), but memantine did not influence CBF and EPSP. Moreover, treatment with memantine increased acetylcholine levels, which was lower in KKAy compared to wild-type mice, and that C21 treatment enhanced memantine-induced acetylcholine secretion.

Research Products

• [Journal Article] Possible synergistic effect of direct angiotensin II type 2 receptor stimulation by compound 21 with memantine on prevention of cognitive decline in type 2 diabetic mice (2013)
  • Author(s): Iwanami J, Mogi M, Tsukuda K, Jing F, Ohshima K, Wang XL, Nakaoka H, Kan-No H, Chisaka T, Bai HY, Min LJ, Horiuchi M
  • Journal Title: Eur J Pharmacol Volume: 724C Pages: 9-15
  • DOI: 10.1016/j.ejphar.2013.12.015
  • Peer Reviewed
• [Presentation] レニン・アンジオテンシン系制御に着目した血管性認知機能障害に対する治療戦略 (2014)
  • Author(s): 岩波純, 茂木正樹, 堀内正嗣
  • Organizer: 第39回日本脳卒中学会
  • Place of Presentation: 大阪国際会議場, 大阪
  • Year and Date: 20140313-15
• [Presentation] AT2 受容体刺激とNMDA 受容体調節による糖尿病性認知機能低下の改善効果 (2013)
  • Author(s): 岩波純, 茂木正樹, 王小俐, 佃架奈, 中岡裕智, 大島弘世, 千阪俊行, Bai Hui-Yu, 菅野晴美, 閔莉娟, 堀内正嗣
  • Organizer: 第36回日本高血圧学会総会
  • Place of Presentation: 大阪国際会議場, 大阪
  • Year and Date: 20131024-26
• [Presentation] 糖尿病モデルマウスにおけるAT2 受容体とNMDA 受容体の相互作用による認知機能低下改善効果 (2012)
  • Author(s): 岩波純, 茂木正樹, 閔莉娟, 佃架奈, 景斐, 大島弘世, 堀内正嗣
  • Organizer: 第35回日本高血圧学会総会
  • Place of Presentation: ウエスティンナゴヤキャッスル, 名古屋市
  • Year and Date: 20120920-22
• [Presentation] 慢性脳低灌流による認知機能低下へのAT2 受容体アゴニストの効果 (2012)
  • Author(s): 岩波純, 茂木正樹, 閔莉娟, 佃架奈, 景斐, 大島弘世, 堀内正嗣
  • Organizer: 第35回日本高血圧学会総会
  • Place of Presentation: ウエスティンナゴヤキャッスル, 名古屋市
  • Year and Date: 20120920-22