Epigenetics analysis in abnormal behavior through dopamin receptors

• Project/Area Number: 21890281
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Ritsumeikan University
• Principal Investigator: INDEN Masatoshi Ritsumeikan University, 薬学部, 助教 (70512424)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,652,000 (Direct Cost: ¥2,040,000、Indirect Cost: ¥612,000); Fiscal Year 2010: ¥1,261,000 (Direct Cost: ¥970,000、Indirect Cost: ¥291,000); Fiscal Year 2009: ¥1,391,000 (Direct Cost: ¥1,070,000、Indirect Cost: ¥321,000)
• Keywords: パーキンソン病 / ドパミン神経 / セロトニン神経 / 6-hydroxydopamine / フルオキセチン / L-dopa / リン酸化ヒストンH3 / 線条体

Research Abstract

In this study, we demonstrated that pre-treatment with fluoxetine, an SSRIs, significantly suppressed L-DOPA-induced ERK1/2 and histone H3 phosphorylation, as well as L-DOPA-induced rotational behavior in 6-OHDA-lesioned rats. These data indicate that L-DOPA-derived DA, released as a "false transmitter" from 5-HT terminals, enhances levels of phosphorylated ERK and histone H3, and this results in abnormal behavior. Fluoxetine may attenuate these effects of a false transmitter via 5-HT receptor. In further support of this supposition, these effects of fluoxetine were abolished by pre-treatment with WAY 100135, a 5-HT1A antagonist.
These results suggest that fluoxetine may influence motor function in PD via pharmacological modification of interactions between serotonergic and dopaminergic neuronal networks.

Research Products

• [Journal Article] Detoxification of 6-hydroxydopamine induced Parkinsonian neurodegeneration by G-CYPMPO, a novel radical trapper. (2011)
  • Author(s): Kitamura Y, Kamibayashi M, Inden M, Yanagida T, Shibaike T, Takata K, Yasui H, Yamashita M, Taniguchi T
  • Journal Title: Neurochem Int 58 Pages: 721-727
  • Peer Reviewed
• [Journal Article] Parkinsonian rotenone mouse model : reevaluation of long-term administration of rotenone in C57BL/6 mice. (2011)
  • Author(s): Inden M, Kitamura Y, Abe M, Tamaki A, Takata K, Taniguchi T
  • Journal Title: Biol Pharm Bull 34 Pages: 92-96
  • NAID: 130000402269
  • Peer Reviewed
• [Journal Article] Detoxification of 6-hydroxydopamine-induced Parkinsonian neurodegeneration by G-CYPMPO, a novel radical trapper. (2011)
  • Author(s): Kitamura, et al.
  • Journal Title: Neurochem Int. Volume: 58 Pages: 721-727
  • Peer Reviewed
• [Journal Article] Parkinsonian rotenone mouse model : reevaluation of long-term administration of rotenone in C57BL/6 mice. (2011)
  • Author(s): Inden, et al.
  • Journal Title: Biol Pharm Bull. Volume: 34 Pages: 92-96
  • NAID: 130000402269
  • Peer Reviewed
• [Journal Article] The 6-hydroxydopamine-induced nigrostriatal neurodegeneration produces microglia-like NG2 glial cells in the rat substantia nigra. (2010)
  • Author(s): Kitamura Y, Inden M, Minamino H, Abe M, Takata K, Taniguchi T
  • Journal Title: Glia 58 Pages: 1686-1700
  • Peer Reviewed
• [Journal Article] The 6-hydroxydopamine-induced nigrostriatal neurodegeneration produces microglia-like NG2 glial cells in the rat substantia nigra. (2010)
  • Author(s): Kitamura, et al.
  • Journal Title: Glia Volume: 58 Pages: 1686-1700
  • Peer Reviewed
• [Journal Article] Adenosine A2A receptor agonist attenuates HDAC inhibitor-induced cell death through the activation of ERK and Akt in PC12 cells. (2009)
  • Author(s): Inden M, Uozumi A, Tsujiko K, Iwata S, Matsui H, Fujioka H, Murata R, Fujita N
  • Journal Title: Current Topics in Pharmacology 13 Pages: 13-23
  • Peer Reviewed
• [Journal Article] Adenosine A2A receptor agonist attenuates HDAC inhibitor-induced cell death through the activation of ERK and Akt in PC12 cells (2009)
  • Author(s): Inden, et al.
  • Journal Title: Current Topics in Pharmacology 13 Pages: 13-22
  • Peer Reviewed
• [Presentation] パーキンソン病モデルラットにおける運動機能へのセロトニン神経関連薬の影響 (2011)
  • Author(s): 位田雅俊,高田和幸,谷口隆之,北村佳久
  • Organizer: 第34回日本神経科学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Presentation] パーキンソン病モデルラットにおける運動機能へのセロトニン神経関連薬の影響 (2011)
  • Author(s): 位田雅俊, 他3名
  • Organizer: 第34回日本神経科学会
  • Place of Presentation: パシフィコ横浜(神奈川県)(発表確定)
• [Presentation] Adenosine A2A receptor agonist protects PC12 cells from histonedeacetylase inhibitor-induced cell death by activating ERK and Akt pathways. (2010)
  • Author(s): 魚住暁,位田雅俊,村田理沙,藤岡洋美,藤田典久
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪国際会議場(大阪府)
• [Presentation] Adenosine A_<2A> receptor agonist protects PC12 cells from histonedeacetylase inhibitor-induced cell death by activating ERK and Akt pathways (2010)
  • Author(s): 魚住暁, ら, 他4名
  • Organizer: 第83回 日本薬理学会年会
  • Place of Presentation: 大阪国際会議場(大阪府)