Bi-phasic change in BDNF gene expression following antidepressant drug treatment
Bi-phasic change in BDNF gene expression following antidepressant drug treatment
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DOI：
10.1016/s0028-3908(03)00077-7
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发表时间：
2003-06-01
影响因子：
4.7
通讯作者：
Zetterström, TSC
中科院分区：
文献类型：
--
作者：
Coppell, AL;Pei, Q;Zetterström, TSC
脑源性神经营养因子（BDNF）基因最近受到关注，与抗抑郁治疗的治疗作用有关。本研究旨在阐明急性和反复抗抑郁药物治疗后间隔时间对大鼠脑内BDNF基因表达的影响。结果发现，重复给予单胺氧化酶抑制剂反苯环丙胺（TCP）或5-羟色胺（5-HT）再摄取抑制剂（氟西汀，帕罗西汀和舍曲林），引起双相和时间依赖性的影响BDNF基因表达在大鼠海马（特别是齿状回）。在最后一次每日两次注射14天后，在4小时（TCP和氟西汀）检测到BDNF基因的下调，在24小时（TCP，帕罗西汀，氟西汀，舍曲林）检测到BDNF基因的上调。单次注射后，在4小时检测到下调（TCP、氟西汀、帕罗西汀和舍曲林），但在给药后24小时（TCP、氟西汀和帕罗西汀），脑源性神经营养因子mRNA水平没有改变。去甲肾上腺素再摄取抑制剂（地昔帕明和马普替林）或非典型抗抑郁药米安色林的管理对BDNF mRNA水平没有影响，无论是在单一（4小时后的药物，地昔帕明）或重复（24小时后的药物，地昔帕明，马普替林，米安色林）治疗。NT-3的基因表达，这是分布在齿状回中的高密度，不受单次或重复注射抗抑郁药（TCP，氟西汀，帕罗西汀，舍曲林，地昔帕明，马普替林或米安色林）在4或24小时后的药物。总之，这些数据表明，抗抑郁药物对BDNF基因表达的影响可能比以前认为的更复杂，而且在治疗中的分布范围更小。因此，在这项研究中，与中央5-HT系统相互作用的药物改变了BDNF的表达，但在给药后24小时内，这种作用是双相的。(C)2003年由Elsevier Science Ltd.出版
The gene for brain derived neurotrophic factor (BDNF) has recently received attention in relation to the therapeutic action of antidepressant treatment. This study aimed to clarify the influence of post drug interval on the effect of acute and repeated treatment with antidepressant drugs on BDNF gene expression in the rat brain. It was found that repeated administration of either the monoamine oxidase inhibitor tranylcypromine (TCP) or 5-hydroxytryptamine (5-HT) re-uptake inhibitors (fluoxetine, paroxetine and sertraline), evoke a bi-phasic and time-dependent effect on BDNF gene expression in the rat hippocampus (especially dentate gyrus). A down-regulation of the BDNF gene was detected at 4 h (TCP and fluoxetine) and an up-regulation at 24 h (TCP, paroxetine, fluoxetine, sertraline) after the last of twice daily injections for 14 days. After a single injection the down-regulation was detected at 4 h (TCP, fluoxetine, paroxetine and sertraline) but BDNF mRNA levels were not altered at 24 h post drug (TCP, fluoxetine and paroxetine). Administration of inhibitors of noradrenaline re-uptake (desipramine and maprotiline) or the atypical antidepressant mianserin had no effect on BDNF mRNA levels at either single (4 h post drug, desipramine) or repeated (24 h post drug, desipramine, maprotiline, mianserin) treatment. The gene expression for NT-3, which is distributed in a high density in the dentate gyrus, was not affected by single or repeated injections of antidepressant drugs (TCP, fluoxetine, paroxetine, sertraline, desipramine, maprotiline or mianserin) at 4 or 24 h post drug. In conclusion, these data show that the effect of antidepressant drugs on BDNF gene expression may be more complex and less widespread across treatments than previously thought. Thus, in this study drugs interacting with the central 5-HT system altered BDNF expression but the effect was bi-phasic over the 24 h post drug period. (C) 2003 Published by Elsevier Science Ltd.