Epigenetics analysis in abnormal behavior through dopamin receptors

通过多巴胺受体进行异常行为的表观遗传学分析

• 批准号: 21890281
• 负责人: INDEN Masatoshi
• 金额: $ 1.7万
• 依托单位: Ritsumeikan University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21890281/
• 关键词: 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

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.

在这项研究中，我们证明了氟西汀（一种SSRIs）预处理可以显著抑制l - dopa诱导的ERK1/2和组蛋白H3磷酸化，以及l - dopa诱导的6- ohda损伤大鼠的旋转行为。这些数据表明，l - dopa衍生的DA作为“假递质”从5-HT末端释放，提高磷酸化的ERK和组蛋白H3的水平，从而导致异常行为。氟西汀可以通过5-羟色胺受体减弱假递质的这些作用。为了进一步支持这一假设，氟西汀的这些作用可以通过5-HT1A拮抗剂WAY 100135预处理而消除。这些结果表明氟西汀可能通过药理学改变血清素和多巴胺能神经元网络之间的相互作用来影响帕金森病的运动功能。

项目成果

The 6-Hydroxydopamine-induced Nigrostriatal Neurodegeneration Produces Microglia-like NG2 Glial Cells in the Rat Substantia Nigra

• DOI: 10.1002/glia.21040
• 发表时间: 2010-11-01
• 期刊: GLIA
• 影响因子: 6.2
• 作者: Kitamura, Yoshihisa;Inden, Masatoshi;Taniguchi, Takashi
• 通讯作者: Taniguchi, Takashi

Detoxification of 6-hydroxydopamine-induced Parkinsonian neurodegeneration by G-CYPMPO, a novel radical trapper.

G-CYPMPO（一种新型自由基捕获剂）对 6-羟基多巴胺诱导的帕金森神经变性的解毒作用。

• 发表时间: 2011
• 期刊: Neurochem Int.
• 作者: Kitamura;et al.
• 通讯作者: et al.

Adenosine A2A receptor agonist attenuates HDAC inhibitor-induced cell death through the activation of ERK and Akt in PC12 cells

腺苷 A2A 受体激动剂通过激活 PC12 细胞中的 ERK 和 Akt 来减轻 HDAC 抑制剂诱导的细胞死亡

• 发表时间: 2009
• 期刊: Current Topics in Pharmacology 13
• 作者: Inden;et al.
• 通讯作者: et al.

Parkinsonian Rotenone Mouse Model: Reevaluation of Long-Term Administration of Rotenone in C57BL/6 Mice

• DOI: 10.1248/bpb.34.92
• 发表时间: 2011-01-01
• 期刊: BIOLOGICAL & PHARMACEUTICAL BULLETIN
• 影响因子: 2
• 作者: Inden, Masatoshi;Kitamura, Yoshihisa;Taniguchi, Takashi
• 通讯作者: Taniguchi, Takashi

Adenosine A2A receptor agonist protects PC12 cells from histonedeacetylase inhibitor-induced cell death by activating ERK and Akt pathways.

腺苷 A2A 受体激动剂通过激活 ERK 和 Akt 途径保护 PC12 细胞免受组蛋白脱乙酰酶抑制剂诱导的细胞死亡。

• 发表时间: 2010
• 作者: Yoshinori Okamoto;他7名;魚住暁,位田雅俊,村田理沙,藤岡洋美,藤田典久
• 通讯作者: 魚住暁,位田雅俊,村田理沙,藤岡洋美,藤田典久