Comprehensive Molecular Genetics to Elucidate The Mechanism of Action of Mood Stabilizers

• Project/Area Number: 19390300
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Tohoku University
• Principal Investigator: TOMITA Hiroaki Tohoku University, 大学院・医学系研究科, 准教授 (90295064)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2008: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000); Fiscal Year 2007: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
• Keywords: 精神薬理学 / 気分調整薬 / 気分安定薬 / リチウム / 双極性障害 / 遺伝子発現 / 機能ゲノム / マイクロアレイ / ゲノム創薬

Research Abstract

躁うつ病(双極性障害)の治療薬(気分調整薬)が効く機構を解明してより有効な薬剤の開発に繋げるため、主な気分調整薬4剤を脳内細胞に由来する培養細胞3種に投与後、各細胞の数万種の遺伝子の発現量を測定し、薬剤間で共通に発現変化を受ける遺伝子を特定した。更に末梢血の単球に気分調整薬を投与し脳内変化に関連する発現変化の特定を行った。これらの知見により気分調整薬の奏効機序に関わる機構の解明が進むと期待される。

Research Products

• [Journal Article] 気分安定薬奏功機序解明のための包括的遺伝子発現解析 (2009)
  • Author(s): 富田博秋, 田中千秋, 兪志前, 小松浩, 木村好, 曽良一郎, Helen B.Kim, William E, Bunney
  • Journal Title: 臨床薬理の進歩 30
• [Journal Article] 気分障害の網羅的遺伝子発現解析 (2009)
  • Author(s): 富田博秋
  • Journal Title: 医学のあゆみ 229(3) Pages: 8121-8125
• [Journal Article] 気分障害の網羅的遺伝子発現解析 (2009)
  • Author(s): 富田博秋
  • Journal Title: 医学のあゆみ 229 Pages: 8121-8125
• [Journal Article] 気分安定薬奏功機序解明のための包括的遺伝子発現解析 (2009)
  • Author(s): 富田博秋、田中千秋、兪志前、小松浩、木村好、曽良一郎、Helen B. Kim, William E. Bunney
  • Journal Title: 臨床薬理の進歩 30(In press)
• [Journal Article] 精神疾患研究におけるミトコンドリア関連遺伝子の発現変化-病態か、アーチファクトか? (2008)
  • Author(s): 富田博秋, 田中千晶
  • Journal Title: 脳と精神の医学 19(2) Pages: 97-106
  • NAID: 10026932978
• [Journal Article] 精神疾患研究におけるミトコンドリア関連遺伝子の発現変化〜病態か、アーチファクトか (2008)
  • Author(s): 富田博秋、田中千晶
  • Journal Title: 脳と精神の医学 19 Pages: 97-106
  • NAID: 10026932978
• [Journal Article] Methodological considerations for gene expression profiling of human brain (2007)
  • Author(s): Atz M, Walsh D, Cartagena P, Li J, Evans S, Choudary P, Overman K, Stein R, Tomita H, Potkin S, Myers R, Watson SJ, Jones EG, Akil H, Bunney WE Jr, Vawter MP
  • Journal Title: J Neurosci Methods 163(2) Pages: 295-309
  • Peer Reviewed
• [Journal Article] Sample matching by inferred agonal stress in gene expression analyses of the brain (2007)
  • Author(s): Li JZ, Meng F, Tsavaler L, Evans SJ, Choudary PV, Tomita H, Vawter MP, Walsh D,Shokoohi V, Chung T, Bunney WE Jr, Jones EG, Akil H, Watson SJ, Myers RM
  • Journal Title: BMC Genomics 8(1) Pages: 336-336
  • Peer Reviewed
• [Journal Article] Methodological considerations for gene expression profiling of human brain. (2007)
  • Author(s): Atz M, et. al.
  • Journal Title: Journal of Neuroscience Methods 163(2) Pages: 295-309
  • Peer Reviewed
• [Presentation] 気分安定薬リチウムの樹状細胞における遺伝子発現変化の包括的検討 (2009)
  • Author(s): 兪志前, 田中千晶, 小松浩, 木村好一郎, 富田博秋
  • Organizer: 第30回リチウム研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-04-18
• [Presentation] 気分安定薬のアストロサイトにおける遺伝子発現変化の包括的検討 (2009)
  • Author(s): 兪志前, 田中千晶, 小松浩, 高橋怜史, 木村好, 曽良一郎, 富田博秋
  • Organizer: 第31回日本生物学的精神医学会
  • Place of Presentation: 京都
• [Presentation] 気分調整薬がヒト神経由来細胞およびグリア由来細胞の各BDNF転写物バリアント発現量に及ぼす影郷の検討 (2008)
  • Author(s): 小松浩, 田中千晶, 兪志前, 木村好, 高橋怜, 曽良一郎, 松岡洋夫, 富田博秋
  • Organizer: 第30回日本生物学的精神医学会
  • Place of Presentation: 富山
  • Year and Date: 2008-09-11
• [Presentation] ゲノム精神医学の現状と明日-統合失調症・気分障害から消化器心身症まで- (2008)
  • Author(s): 富田博秋
  • Organizer: 東三河消化器病懇話会学術講演会
  • Place of Presentation: 豊橋
  • Year and Date: 2008-05-10
• [Presentation] 気分安定薬-開発と奏効機序研究の歴史と現状- (2008)
  • Author(s): 富田博秋
  • Organizer: 第65回石川県神経科精神科医学会学術講演会
  • Place of Presentation: 金沢
  • Year and Date: 2008-04-10
• [Presentation] 気分安定薬は双極性障害に何故効くのか?-基本から最新の研究情報まで- (2008)
  • Author(s): 富田博秋
  • Organizer: デパケン双極性障害適応拡大5周年記念講演会
  • Place of Presentation: 仙台
  • Year and Date: 2008-02-01
• [Presentation] 気分安定薬は双極性障害に何故効くのか?〜基本から最新の研究情報まで〜 (2008)
  • Author(s): 富田 博秋
  • Organizer: デパケン双極性障害適応拡大5周年記念講演会
  • Place of Presentation: 仙台市
  • Year and Date: 2008-02-01
• [Presentation] Time-dependent genome-wide gene expression study of neural cells after lithium treatment (2008)
  • Author(s): Takahashi S, Tanaka C, Yu Z, Kimura K, Sora I, Tomita H
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
• [Presentation] Effect of mood stabilizers on genome-wide gene expression profiles of human CNS-derived cell lines. Symposium "Genome-wide studies of bipolar disorder and mood stabilizaion" (2008)
  • Author(s): Tomita H
  • Organizer: World Congress of Psychiatric Genetics 15th annual meeting
  • Place of Presentation: Osaka, Japan
• [Presentation] 双極性障害治療薬の神経細胞およびグリア細胞における遺伝子発現変化の包括的検討 (2008)
  • Author(s): 兪志前, 田中千晶, 小松浩, 高橋怜史, 木村好, 富田博秋
  • Organizer: 第53回日本人類遺伝学会
  • Place of Presentation: 横浜
• [Presentation] Microarray gene expression profiles in neuronal and glial cell lines after lithium, valproate, carbamazepine and lamotrigine treatment (2008)
  • Author(s): Yu Z, Tanaka C, Komatsu H, Takahashi S, Kim HB, Kimura K, Sora I, Bunney WE, Tomita H
  • Organizer: World Federation of Societies of Biological Psychiatry 2nd Asia-Pacific Congress
  • Place of Presentation: Toyama, Japan
• [Presentation] 神経細胞およびグリア細胞における遺伝子発現プロファイルへのリチウムの影響 (2008)
  • Author(s): 富田博秋, 田中千秋, Helen B. Kim, William E. Bunney
  • Organizer: 第31回日本神経科学会
  • Place of Presentation: 東京
• [Presentation] Neuron- and glia- specific gene expression profiles after lithium treatment (2008)
  • Author(s): Tomita H, Tanaka C, Kim HB, Bunney WE
  • Organizer: Collegium internationale neuro-psychopharmacologicum 50th congress
  • Place of Presentation: Munich, Germany
• [Presentation] Effect of mood stabilizers on genome-wide gene expression profiles of human CNS-derived cell lines. Symposium "Genome-wide studies of bipolar disorder and mood stabilizaion" (2008)
  • Author(s): Tomita H.
  • Organizer: World Congress of Psychiatric Genetics 15th annual meeting
  • Place of Presentation: Osaka, Japan.
• [Presentation] Neuron-and glia-specific gene expression profiles after lithium treatment (2008)
  • Author(s): Tomita H, Tanaka C, Kim HB, Bunney WE.
  • Organizer: World Congress of Psychiatric Genetics 15th annual meeting
  • Place of Presentation: Osaka, Japan.
• [Presentation] Microarray gene expression profiles in neuronal and glial cell lines after lithium, valproate, carbamazepine and lamotrigine treatment (2008)
  • Author(s): Yu Z, Tanaka C, Komatsu H, Takahashi S, Kim HB, Kimura K, Sora I, Bunney WE, Tomita H.
  • Organizer: World Federation of Societies of Biological Psychiatry 2nd Asia-Pacific Congress,
  • Place of Presentation: Toyama, Japan.
• [Presentation] Expression profiles of BDNF transcript variants in neuronal and glial cell lines after treatment with mood stabilizers (2008)
  • Author(s): Komatsu H, Tanaka C, Yu Z, Kimura K, Takahashi S, Sora I, Matsuoka H, Tomita H.
  • Organizer: World Congress of Psychiatric Genetics 15th annual meeting
  • Place of Presentation: Osaka, Japan.
• [Presentation] Microarray gene expression profiles in neuronal and glial cell lines after lithium, valproate, carbamazepine and lamotrigine treatment (2008)
  • Author(s): Yu Z, Tanaka C, Komatsu H, Takahashi S, Kim HB, Kimura K, Sora I, Bunnev WE, Tomita H.
  • Organizer: Society for Neuroscience 38th annual meeting
  • Place of Presentation: Washington DC, USA
• [Presentation] Microarray gene expression analyses of neurons, astrocytes and, oligod endrocytes, and neurons after mood stabilizer treatment (2008)
  • Author(s): Yu Z, Tanaka C, Komatu H, Takahashi S, Kimura K, Sora I, Tomita H
  • Organizer: Tohoku University-Fudan University Neuroscience Workshop for Young Scientists
  • Place of Presentation: Shanghai, China
• [Presentation] Time-dependent genome-wide gene expression study of neural cells after lithium treatment (2008)
  • Author(s): Takahashi S, Tanaka C, Yu Z, Kimura K, Sora I, Tomita H
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] Microarray gen expression profiles in neuronal and glial cell lines after lithium treatment (2007)
  • Author(s): Tomita H, Tanaka C, Kim HB, Bunney WE
  • Organizer: Society for Neuroscience 37th annual meeting
  • Place of Presentation: San Diego CA., USA
• [Presentation] Microarray gene expression profiles in neuronal and gilial cell linesafterlithiumtreatment. (2007)
  • Author(s): Tomita H, et. al.
  • Organizer: Society for Neuroscience 37th annual meeting
  • Place of Presentation: San Diego, CA., USA.