A study of new drug development of target of histone deacetylase

• Project/Area Number: 23791336
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Yamaguchi University
• Principal Investigator: OTUKI Kouji 山口大学, 大学院・医学系研究科, 助教 (10535256)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: GDNF / HDAC4 / エピジェネティクス

Research Abstract

Interestingly, HDAC4 significantly inhibited the induction of GDNF mRNA by antidepressants. Therefore the level of phosphorylation of HDAC4 was increased by antidepressants. In the animal syudy, mutant HDAC4 was suggested that antidepressant effect.

Research Products

• [Journal Article] The alteration of hypoxia inducible facter-1 (HIF-1) and its target genenes in mood disorder patients (2013)
  • Author(s): Shibata T, Yamagata H, Uchida S, Otsuki K, Hobara T, Higuchi F, Abe N, & Watanabe Y
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 43 Pages: 222-229
  • Peer Reviewed
• [Journal Article] State-dependent changes in the expression of DNA methyltransferases in mood disorder patients (2012)
  • Author(s): Higuchi F, Uchida S, Otsuki K, Hobara T, Abe N, Yamagata H, Shibata T, & Watanabe Y
  • Journal Title: J Psychiatr Res Volume: 45 Pages: 1295-1300
  • Peer Reviewed
• [Journal Article] Altered sirtuin deacetylase gene expression in patients with a mood disorder (2012)
  • Author(s): Abe N, Uchida S, Otsuki K, Hobara T, Yamagata H, Higuchi F, Shibata T, & Watanabe Y
  • Journal Title: J Psychiatr Res Volume: 45 Pages: 1106-1112
  • Peer Reviewed
• [Journal Article] 気分障害のバイオマーカー開発、とくに白血球での遺伝子発現からみた気分障害の状態診断、亜型分類 (2012)
  • Author(s): 渡邉義文、内田周作、大朏孝治、山形弘隆、芳原輝之、阿部尚子、樋口文宏、綿貫俊夫、松原敏郎
  • Journal Title: 精神神経学雑誌 Volume: 114 Pages: 812-820
  • NAID: 10030970858
  • Peer Reviewed
• [Journal Article] うつ病におけるエピジェネティクス (2012)
  • Author(s): 大朏孝治、内田周作、芳原輝之、山形弘隆、渡邉義文
  • Journal Title: 日本神経薬理学雑誌 Volume: 32 Pages: 181-186
  • NAID: 10031055656
• [Journal Article] ヒストン脱アセチル化酵素阻害剤の早期抗うつ効果発現における分子機構の解析 (2012)
  • Author(s): 芳原輝之、内田周作、山形弘隆、大朏孝治、渡邉義文
  • Journal Title: 日本生物学的精神医学会誌 Volume: 23 Pages: 35-40
  • NAID: 130005395372
• [Journal Article] うつ病とエピジェネティクス (2012)
  • Author(s): 山形弘隆、内田周作、芳原輝之、大朏孝治、渡邉義文
  • Journal Title: 精神科 Volume: 20 Pages: 632-38
  • NAID: 10029785558
• [Journal Article] うつ病とエピジェネティクス (2011)
  • Author(s): 大朏孝治、内田周作、芳原輝之、渡辺義文
  • Journal Title: 日本生物学的精神医学会誌 Volume: 22 Pages: 89-95
  • NAID: 10029785558
• [Journal Article] Impaired hippocampal spinogenesis and neurogenesis and altered affective behavior in mice lacking heat shock factor 1 (2011)
  • Author(s): Uchida S, Hara K, Kobayashi A, Fujimoto M, Otsuki K, Yamagata H, Hobara T, Abe N, Higuchi F, Shibata T, Hasegawa S, Kida S, Nakai A, & Watanabe Y
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 108 Pages: 1681-1686
  • Peer Reviewed
• [Journal Article] Epigenetic status of Gdnf in the ventral striatum determines susceptibility and adaptation to daily stressful events (2011)
  • Author(s): Uchida S, Hara K, Kobayashi A, Otsuki K, Yamagata H, Hobara T, Suzuki T, Miyata N, & Watanabe Y
  • Journal Title: Neuron Volume: 69 Pages: 359-372
  • Peer Reviewed
• [Presentation] The mechanism of GDNF transcriptional regulation by antidepressants through HDAC4 (2012)
  • Author(s): Koji Otsuki, Shusaku Uchida, Hirotaka Yamagata and Yoshifumi Watanabe
  • Organizer: 第34回日本神経科学会
  • Place of Presentation: 神戸国際会議場(神戸)
  • Year and Date: 2012-09-30
• [Presentation] HDAC4を介した抗うつ薬によるGDNF遺伝子転写制御のメカニズム (2012)
  • Author(s): 大朏孝治, 内田周作, 芳原輝之, 山形弘隆, 渡邉義文
  • Organizer: 第34回生物学的精神医学会
  • Place of Presentation: 神戸コンベンションセンター(神戸)
• [Presentation] Epigenetic regulation in depression (2011)
  • Author(s): Koji Otsuki, Shusaku Uchida, Teruyuki Hobara, Hirotaka Yamagata and Yoshifumi Watanabe
  • Organizer: 第41回日本神経精神薬理学会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2011-10-28
• [Presentation] Epigenetic mechanisms of GDNF expression involved in the stress vulnerability and depression (2011)
  • Author(s): Koji Otsuki, Shusaku Uchida, Teruyuki Hobara, Hirotaka Yamagata and Yoshifumi Watanabe
  • Organizer: 第32回内籐財団コンファレンス
  • Place of Presentation: 八ヶ岳ロイヤルホテル(山梨)
  • Year and Date: 2011-10-19
• [Presentation] Epigenetic regulation in depression
  • Author(s): Koji Otsuki, Shusaku Uchida, Teruyuki Hobara, Hirotaka Yamagata and Yoshifumi Watanabe
  • Organizer: 第41回日本神経精神薬理学会
  • Place of Presentation: 京王プラザホテル（東京）
• [Book] 精神疾患診断のための脳形態・機能検査法 (2012)
  • Author(s): 大朏孝治、内田周作、渡辺義文
  • Publisher: 新興医学出版社
• [Book] 末梢白血球に発現している遺伝子と気分障害, 精神疾患診断のための脳形態・機能検査法 (2011)
  • Author(s): 大朏孝治、内田周作、渡辺義文
  • Publisher: 新興医学出版社