The Mechanism of neuroplasticity for discovery of antidepressants

• Project/Area Number: 22791127
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: Yamaguchi University
• Principal Investigator: YAMAGATA Hirotaka 山口大学, 大学院・医学系研究科, 助教 (10549934)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 精神薬理学 / 神経可塑性 / うつ病

Research Abstract

Antidepressant treatment has been reported to increase neurogenesis and neural plasticity in the hippocampus. In this study, we focused on BubR1. The mRNA of BubR1 was decreased with chronic antidepressant treatment in the hippocampus the model mice for depression. Silencing of BubR1 accelerated neurite outgrowth in Neuro2a and SH-SY5Y cells. Exogenous expression of BubR1 inhibited neurite outgrowth in Neuro2a cells and primary neuron. These results suggest that BubR1 might be involved in the neural plasticity and the effect of antidepressant.

Research Products

• [Journal Article] State-dependent changes in the expression of DNA methyltransferases in mood disorder patients (2011)
  • Author(s): Higuchi F, Uchida S, Yamagata H, Otsuki K, Hobara T, Abe N, Shibata T, Watanabe Y
  • Journal Title: J Psychiatr Res Volume: 45 Pages: 1295-300
  • Peer Reviewed
• [Journal Article] Altered sirtuin deacetylase gene expression in patients with a mood disorder (2011)
  • 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: 1106-12
  • Peer Reviewed
• [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 USA Volume: 108 Pages: 1681-6
  • 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, and Watanabe Y
  • Journal Title: Neuron Volume: 69 Pages: 359-72
  • Peer Reviewed
• [Journal Article] State-dependent changes in the expression of DNA methyltransferases in mood disorder patients (2011)
  • Author(s): Fumihiro Higuchi, et al
  • Journal Title: J Psychiatr Res Volume: 45(10) Issue: 10 Pages: 1295-300
  • DOI: 10.1016/j.jpsychires.2011.04.008
  • Peer Reviewed
• [Journal Article] Impaired hippocampal spinogenesis and neurogenesis and altered affective behavior in mice lacking heat shock factor 1 (2011)
  • Author(s): Shusaku Uchida, et al.
  • 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): Shusaku Uchida, et al.
  • Journal Title: Neuron Volume: 69 Pages: 359-372
  • Peer Reviewed
• [Journal Article] Early life stress enhances behavioral vulnerability to stress through the activation of REST4-mediated gene transcription in the medial prefrontal cortex of rodents (2011)
  • Author(s): Shusaku Uchida, et al.
  • Journal Title: J Neurosci Volume: 30 Pages: 15007-15018
  • Peer Reviewed
• [Journal Article] Altered sirtuin deacetylase gene expression in patients with a mood disorder (2011)
  • Author(s): Naoko Abe, et al.
  • Journal Title: J Psychiatr Res Volume: (in press)
  • Peer Reviewed
• [Journal Article] Early life stress enhances behavioral vulnerability to stress through the activation of REST4-mediated gene transcription in the medial prefrontal cortex of rodents (2010)
  • Author(s): Uchida S, Hara K, Kobayashi A, Funato H, Hobara T, Otsuki K, Yamagata H, McEwen BS, Watanabe Y
  • Journal Title: J Neurosci Volume: 30 Pages: 15007-18
  • Peer Reviewed
• [Presentation] Molecular mechanisms of rapid antidepressant action by SAHA (2011)
  • Author(s): Teruyuki Hobara, et al
  • Organizer: Neuroscience 2011
  • Place of Presentation: Washington, DC.USA
  • Year and Date: 2011-11-16
• [Presentation] The function of FoxO3-Noxa pathway in depression model mouse (2011)
  • Author(s): Tomohiko Shibata, et al
  • Organizer: Neuroscience 2011
  • Place of Presentation: Washington, DC.USA
  • Year and Date: 2011-11-16
• [Presentation] BubR1 inhibits neurite outgrowth of neuroblastoma cells (2011)
  • Author(s): Hirotaka Yamagata et al
  • Organizer: Neuroscience 2011
  • Place of Presentation: Washington, DC. USA
  • Year and Date: 2011-11-14
• [Presentation] BubR1 inhibits neurite outgrowth of neuroblastoma cells (2011)
  • Author(s): Hirotaka Yamagata, et al
  • Organizer: Neuroscience 2011
  • Place of Presentation: Washington, DC.USA
  • Year and Date: 2011-11-14
• [Presentation] Possible involvement of microRNA-124 in neuronal plasticity and depression-like behavior (2011)
  • Author(s): Fumihiro Higuchi, et al
  • Organizer: Neuroscience 2011
  • Place of Presentation: Washington, DC.USA
  • Year and Date: 2011-11-13
• [Presentation] SIRT1, a histone deacetylase, might be involved in neural plasticity and depression-like behavior (2011)
  • Author(s): Naoko Abe, et al
  • Organizer: Neuroscience 2011
  • Place of Presentation: Washington, DC.USA
  • Year and Date: 2011-11-13
• [Presentation] 気分障害におけるエピジェネティクス (2011)
  • Author(s): 大朏孝治, 他
  • 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(東京都)
  • Year and Date: 2011-10-28
• [Presentation] エピジェネティクスとストレス脆弱性、うつ病 (2011)
  • Author(s): 山形弘隆, 他
  • Organizer: 第54回日本神経化学学会
  • Place of Presentation: 瑠璃光(金沢市)
  • Year and Date: 2011-09-27
• [Presentation] エピジェネティクスとストレス脆弱性、うつ病 (2011)
  • Author(s): 山形弘隆, 他
  • Organizer: 第54回日本神経化学学会
  • Place of Presentation: 瑠璃光(石川県金沢市)
  • Year and Date: 2011-09-27
• [Presentation] BubR1はニューロブラストーマ細胞の神経突起伸展を制御している (2011)
  • Author(s): 山形弘隆, 他
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2011-09-17
• [Presentation] 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 (2011)
  • Author(s): 芳原輝之, 他
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2011-09-17
• [Presentation] ヒストン脱アセチル化酵素SIRT1の神経可塑性とうつ様行動への関与 (2011)
  • Author(s): 阿部尚子, 他
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2011-09-16
• [Presentation] 神経可塑性とうつ様行動におけるmicroRNA-124の役割の解析 (2011)
  • Author(s): 樋口文宏, 他
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2011-09-16
• [Presentation] うつ病モデルマウスの脳におけるFoxO3-Noxa経路の機能について (2011)
  • Author(s): 柴田朋彦, 他
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2011-09-16
• [Presentation] うつ薬はHDAC4によるヒストン修飾を介してGDNF発現量を増加させる (2011)
  • Author(s): 大朏孝治, 他
  • Organizer: 第33回日本生物学的精神医学会
  • Place of Presentation: グランパシフィックLE DAIBA(東京)
  • Year and Date: 2011-05-22
• [Presentation] 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 (2011)
  • Author(s): 芳原輝之, 他
  • Organizer: 第33回日本生物学的精神医学会
  • Place of Presentation: グランパシフィックLE DAIBA(東京)
  • Year and Date: 2011-05-22
• [Presentation] うつ病と神経可塑性に対するBubR1の役割 (2010)
  • Author(s): 山形弘隆, 他
  • Organizer: 第32回日本生物学的精神医学会
  • Place of Presentation: リーガロイヤルホテル小倉(北九州市)
• [Presentation] うつ病と神経可塑性に対するBubR1の役割 (2010)
  • Author(s): 山形弘隆, 他
  • Organizer: 第32回日本生物学的精神医学会
  • Place of Presentation: 小倉 リーガロイヤルホテル小倉
• [Presentation] うつ病モデルマウスおよび大うつ病性障害患者におけるNoxa mRNAの発現変化 (2010)
  • Author(s): 柴田朋彦, 他
  • Organizer: 第32回日本生物学的精神医学会
  • Place of Presentation: 小倉 リーガロイヤルホテル小倉
• [Presentation] ヒストン脱アセチル化酵素阻害剤による抗うつ効果の分子機構の解析 (2010)
  • Author(s): 芳原輝之, 他
  • Organizer: 第32回日本生物学的精神医学会
  • Place of Presentation: 小倉 リーガロイヤルホテル小倉
• [Presentation] Molecular mechanisms of the antidepressant actions by histone deacetylase inhibitors (2010)
  • Author(s): 芳原輝之, 他
  • Organizer: 第33回日本神経科学大会
  • Place of Presentation: 神戸 神戸コンベンションセンター
• [Presentation] 抗うつ薬はHDAC4によるヒストン修飾を介してGDNF遺伝子の転写活性を増加させる (2010)
  • Author(s): 大朏孝治, 他
  • Organizer: 第33回日本神経科学大会
  • Place of Presentation: 神戸 神戸コンベンションセンター
• [Presentation] Antidepressants increase GDNF gene transcription through the histone modifications by HDAC4 (2010)
  • Author(s): Koji Otsuki, et al.
  • Organizer: Neuroscience meeting 2010
  • Place of Presentation: Sandiego USA
• [Presentation] Molecular mechanisms of the antidepressant actions induced by histone deacetylase inhibitors (2010)
  • Author(s): Teruyiki Hobara, et al.
  • Organizer: Neuroscience meeting 2010
  • Place of Presentation: Sandiego USA