Altered RNA editing of serotonin 2C receptor in a rat model of depression
Altered RNA editing of serotonin 2C receptor in a rat model of depression
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DOI：
10.1016/j.neures.2005.06.001
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发表时间：
2005-09-01
影响因子：
2.9
通讯作者：
Kato, T
中科院分区：
文献类型：
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作者：
Iwamoto, K;Nakatani, N;Kato, T
5-羟色胺2C受体（HTR 2C）的RNA编辑改变被认为参与了抑郁症的病理生理学。在这里，我们检查了HTR 2C的RNA编辑状态在习得性无助（LH）大鼠，一个成熟的抑郁症动物模型。LH大鼠表现出E位点RNA编辑显著增加，其他编辑位点RNA编辑也有增加的趋势。氟西汀（一种选择性5-羟色胺再摄取抑制剂）或丙咪嗪（一种三环类抗抑郁药）治疗影响了LH大鼠的RNA编辑状态。尽管这些抗抑郁药差异性地改变了RNA编辑状态，但它们通常降低了E位点的RNA编辑效率。我们进一步揭示，LH大鼠和抗抑郁药中RNA编辑的改变不能通过RNA编辑酶或其底物（作用于RNA的腺苷脱氨酶，HTR 2C和HTR 2C的剪接形式）的表达改变来解释。这些结果表明，HTR 2C的RNA编辑的改变可能在抑郁症的病理生理学和抗抑郁药的作用中发挥作用。(c)2005年Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
Altered RNA editing of serotonin 2C receptor (HTR2C) has been suggested to be involved in the pathophysiology of major depression. Here we examined RNA editing status of HTR2C in the learned helplessness (LH) rats, one of well-established animal models of depression. LH rats showed the significantly increased RNA editing of site E, and tendency for increased RNA editing of other editing sites. Treatment with fluoxetine, a selective serotonin reuptake inhibitor, or imipramine, a tricyclic antidepressant, affected the RNA editing status of the LH rats. Although, these antidepressants differentially altered RNA editing status, they commonly reduced RNA editing efficiency of site E. We further revealed that altered RNA editing in the LH rats and by antidepressants was not explained by altered expression of RNA editing enzymes or their substrates (adenosine deaminases that act on RNA, HTR2C, and spliced form of HTR2C). These results suggest that alteration of RNA editing of HTR2C may play a role in the pathophysiology of depression and action of antidepressants. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.