Effects of drug acting on mitochondrial calcium uptake in model mice for bipolar disorder

• Project/Area Number: 19790844
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: KUBOTA Mie The Institute of Physical and Chemical Research, 精神疾患動態研究チーム, 研究員 (90344035)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: ミトコンドリア / 双極性障害 / 精神薬理学 / mitochondria / polymerase γ / cyclophilin D / cycrosporin A / permeability transition pore / polymeraseγ / calcium signaling

Research Abstract

双極性障害モデル動物である脳内mtDNA変異蓄積マウスを用い、ミトコンドリアのCa2+制御異常を調べたところ、変異マウス脳ミトコンドリアでは、Ca2+取り込み速度亢進が観察された。この分子機構と変異マウスで観察された異常行動との関連について調べるため、CypD阻害剤の輪回し行動に対する影響を検討した。CypD阻害剤を変異マウスに約2週間、連続的に腹腔内投与し、輪回し行動を観察したところ、約1週間後から行動異常は徐々に減少し、2週間後には有意に減少した。ミトコンドリア機能を標的とした薬剤が、新たな奏効機序を持つ気分安定薬候補物質になる可能性が考えられた。

Research Products

• [Presentation] Effects of drug acting on mitochondrial calcium uptak in mutant POLG transgenic mice (2008)
  • Author(s): Mie Kubota
  • Organizer: 2nd World Federation of Societies of Biological Psychiatry Asia-Paific Congress and 30th Annual Meeting of Japan Societies Biological Psychiatry
  • Place of Presentation: Toyama
  • Year and Date: 2008-09-12
• [Presentation] Effects of drug acting on mitochondrial calcium uptake in mutant POLG transgenic mice (2008)
  • Author(s): 窪田美恵
  • Organizer: 日本生物学的精神医学会
  • Place of Presentation: ANAクラウンプラザホテル富山
  • Year and Date: 2008-09-12
• [Presentation] Abnormal mitochondrial Ca^<2+> dynamics and behavioral phenotypes in transgenic mice with mitochondrial DNA defects (2008)
  • Author(s): Mie Kubota
  • Organizer: The 7th European Meeting on Mitochondrial Pathology
  • Place of Presentation: the City Conference Centre Stockholm
  • Year and Date: 2008-07-12
• [Presentation] Abnormal mitochondrial Ca2+ dynamics and behavioral phenotypes in transgenic mice with mitochondrial DNA defects (2008)
  • Author(s): Mie Kubota
  • Organizer: The 7th EuropeanMeeting on Mitochondria Pathology
  • Place of Presentation: Stockholm
  • Year and Date: 2008-06-12
• [Presentation] Gene Expression Profile in the Brain of Animal Model for Bipolar Disorder (2007)
  • Author(s): Mie Kubota
  • Organizer: Cold Spring Harbor Laboratory Meeting Integrative Approaches to Brain Complexity
  • Place of Presentation: Cambridge
  • Year and Date: 2007-09-27
• [Presentation] GENE EXPRESSION PROFILE IN THE BRAIN OF ANIMAL MODELFOR BIPOLAR DISOEDER (2007)
  • Author(s): Mie Kubota
  • Organizer: Cold Spring Harbor Meeting (Integrative Approaches To Brain Complexity)
  • Place of Presentation: The Welcome Trust Conference Center
  • Year and Date: 2007-09-27
• [Presentation] 双極性障害モデル動物における単離ミトコンドリアを用いたカルシウム取り込み脳の薬理学的検討 (2007)
  • Author(s): 窪田 美恵
  • Organizer: 日本生物精神医学会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2007-07-13