Time-dependent biphasic modulation of human BDNF by antidepressants in neuroblastoma cells.
Time-dependent biphasic modulation of human BDNF by antidepressants in neuroblastoma cells.
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DOI：
10.1186/1471-2202-9-61
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发表时间：
2008-07-05
期刊：
影响因子：
2.4
通讯作者：
Popoli M
中科院分区：
文献类型：
--
作者：
Donnici L;Tiraboschi E;Tardito D;Musazzi L;Racagni G;Popoli M
最近的啮齿动物研究报道，抗抑郁治疗通过选择性地调节不同的脑源性神经营养因子转录本，以一种依赖于治疗时间的方式影响脑源性神经营养因子的mRNA的表达。然而，目前还没有关于人类BDNF基因的数据。我们研究了不同的抗抑郁药物对人神经母细胞瘤SH-SY5Y细胞BDNF基因表达的影响。培养的细胞分别用氟西汀、瑞波西汀和地塞帕明处理不同时间(6、24、48h)。逆转录-聚合酶链式反应(RT-PCR)检测总BDNF mRNA的表达，半巢式-聚合酶链式反应检测不同转录物的表达水平。瑞波西汀或地塞帕明短期治疗(6小时)降低总BDNF水平，而长期治疗(48小时)显著增加总BDNF mRNA水平。这些变化是由于BDNFIV和VIA/b转录本的不同调控所致。氟西汀无明显疗效。这是第一个显示抗抑郁药物治疗后人类细胞中总的和特定的BDNF转录本表达的双相变化的研究。这些发现表明，抗抑郁药物对BDNF的双向诱导可能是啮齿类动物和人类的共同特征，并鼓励使用SH-SY5Y细胞作为研究药物对人类基因影响的工具。
Recent rodent studies reported that antidepressant treatments affect the expression of brain-derived neurotrophic factor (BDNF) mRNA in a way that is dependent on treatment duration, by selective modulation of different BDNF transcripts. However, no data are available for the human BDNF gene. We studied the effect of different antidepressants on BDNF mRNA expression in human neuroblastoma SH-SY5Y cells. Cultured cells were treated with the antidepressants fluoxetine, reboxetine and desipramine for different time lengths (6, 24, 48 hours). Expression of total BDNF mRNA was analyzed by reverse transcription PCR and levels of different BDNF transcripts were detected by hemi-nested PCR with specific primers. Short-term treatment (6 hours) with reboxetine or desipramine reduced total BDNF, whereas long-term treatment (48 hours) significantly increased total BDNF mRNA levels. These changes were accounted for by differential regulation of BDNF IV and VIa/b transcripts. Fluoxetine showed no significant effects. This is the first study showing biphasic changes in the expression of total and specific BDNF transcripts in human cells following antidepressant treatments. These findings suggest that biphasic induction of BDNF by antidepressants could be a feature common to rodents and humans and encourage the use of SH-SY5Y cells as a tool for investigation of drug effects on human genes.
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影响因子：
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