tudy of pathological mechanism underlying autism by focusing on nanoscale distribution of synaptic molecules

• Project/Area Number: 15K15048
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: The University of Tokyo
• Principal Investigator: Namiki Shigeyuki 東京大学, 大学院医学系研究科(医学部), 助教 (90452193)
• Co-Investigator(Renkei-kenkyūsha): Hirose Kenzo 東京大学, 大学院医学系研究科, 教授 (00292730)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 精神疾患 / 自閉症 / シナプス / 超解像イメージング

Outline of Final Research Achievements

We developed a superresolution imaging platform for microscopic analysis of synaptic molecules in the brain of psychiatric model animals. We optimized optical systems and experimental conditions for the fluorescence labeling of brain slices of model animals for STORM imaging. We also developed software for analyzing distribution of synaptic molecules in STORM images. STORM analysis of various regions of brain of the model mouse revealed the change in size and number of nanoclusters formed by dopamine receptors in striatum nucleus accumbens of DISC1 knockout mice. We confirmed that alteration of D2R nanoclusters in DISC1 knockout mice was improveed by administration of antipsychotic clozapine.

Research Products

• [Presentation] 統合失調症モデルマウス腹側線条体におけるDRD2空間分布の変容 (2017)
  • Author(s): 大西泰地、並木繁行、廣瀬謙造
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎市
  • Year and Date: 2017-03-15
• [Presentation] 神経伝達物質開口放出におけるシナプス分子ナノアセンブリの機能的役割 (2016)
  • Author(s): 並木繁行
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台市
  • Year and Date: 2016-09-22
  • Invited
• [Presentation] Regulation of synaptic vesicle exocytosis by nanoassembly of synaptic molecules (2016)
  • Author(s): Shigeyuki Namiki，Hirokazu Sakamoto，Tetsuro Ariyoshi，Kenzo Hirose
  • Organizer: 日本神経科学大会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-07-22
  • Invited
• [Presentation] Analysis of synaptic molecular arrangement in a mouse model of schizophrenia (2016)
  • Author(s): 中山 翔太、並木 繁行、坂本 寛和、宮川 剛、廣瀬 謙造
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-03-09
• [Presentation] Subregion-specific alteration of DRD2 expression in the striatum of model mice of schizophrenia. (2016)
  • Author(s): 大西泰地、中山 翔太、並木 繁行、坂本 寛和、廣瀬 謙造
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-03-09