Modulation of serotonin transporter function during fetal development causes dilated heart cardiomyopathy and lifelong behavioral abnormalities.
Modulation of serotonin transporter function during fetal development causes dilated heart cardiomyopathy and lifelong behavioral abnormalities.
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胎儿发育过程中5-羟色胺转运蛋白功能的调节导致心脏病扩张和终身行为异常。
DOI：
10.1371/journal.pone.0002782
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发表时间：
2008-07-23
期刊：
影响因子：
3.7
通讯作者：
Smidt MP
中科院分区：
文献类型：
--
作者：
Noorlander CW;Ververs FF;Nikkels PG;van Echteld CJ;Visser GH;Smidt MP
女性在生育年龄期间患情绪和焦虑症的风险很大，并且可能在服用抗抑郁药物时怀孕。在抑郁症和焦虑症的治疗中，选择性5-羟色胺再摄取抑制剂（SSRIs）是最常见的处方药，但这种药物是否会影响胎儿中枢神经系统的发育在很大程度上是未知的。可能的影响是胎盘转移效率、给药时间和相应SSRI剂量的乘积。为了获得这些信息，我们已经建立了一项研究，其中测量了这些参数，并绘制了生理和行为方面的后果。氟西汀和氟伏沙明（两种常用的SSRI）的胎盘转移在小鼠和人之间相似，表明小鼠中这些SSRI的胎儿暴露与人类情况相当。氟伏沙明显示相对较低的胎盘转移，而氟西汀显示相对较高的胎盘转移。使用临床剂量的氟西汀，后代的死亡率急剧增加，而氟伏沙明暴露后，死亡率不受影响。大多数暴露于氟西汀的后代出生后死于扩张型心肌病引起的严重心力衰竭。对氟西汀暴露后代的分子分析显示中缝核中5-羟色胺转运体水平的长期改变。此外，产前氟西汀暴露导致成年小鼠出现抑郁和焦虑相关行为。相比之下，氟伏沙明暴露的小鼠没有表现出行为和5-羟色胺转运蛋白水平的改变。降低氟西汀的剂量可以提高存活率，并且对后代的长期行为影响较小。这些结果表明，产前氟西汀暴露影响胎儿发育，导致心肌病和情感障碍的易感性更高，呈剂量依赖性。
Women are at great risk for mood and anxiety disorders during their childbearing years and may become pregnant while taking antidepressant drugs. In the treatment of depression and anxiety disorders, selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed drugs, while it is largely unknown whether this medication affects the development of the central nervous system of the fetus. The possible effects are the product of placental transfer efficiency, time of administration and dose of the respective SSRI. In order to attain this information we have setup a study in which these parameters were measured and the consequences in terms of physiology and behavior are mapped. The placental transfer of fluoxetine and fluvoxamine, two commonly used SSRIs, was similar between mouse and human, indicating that the fetal exposure of these SSRIs in mice is comparable with the human situation. Fluvoxamine displayed a relatively low placental transfer, while fluoxetine showed a relatively high placental transfer. Using clinical doses of fluoxetine the mortality of the offspring increased dramatically, whereas the mortality was unaffected after fluvoxamine exposure. The majority of the fluoxetine-exposed offspring died postnatally of severe heart failure caused by dilated cardiomyopathy. Molecular analysis of fluoxetine-exposed offspring showed long-term alterations in serotonin transporter levels in the raphe nucleus. Furthermore, prenatal fluoxetine exposure resulted in depressive- and anxiety-related behavior in adult mice. In contrast, fluvoxamine-exposed mice did not show alterations in behavior and serotonin transporter levels. Decreasing the dose of fluoxetine resulted in higher survival rates and less dramatic effects on the long-term behavior in the offspring. These results indicate that prenatal fluoxetine exposure affects fetal development, resulting in cardiomyopathy and a higher vulnerability to affective disorders in a dose-dependent manner.
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影响因子：
56.9
作者：
Santarelli, L;Saxe, M;Hen, R
通讯作者：
Hen, R
影响因子：
10.6
作者：
Holmes, A;Murphy, DL;Crawley, JN
通讯作者：
Crawley, JN
影响因子：
37.8
作者：
Nebigil, CG;Hickel, P;Maroteaux, L
通讯作者：
Maroteaux, L
影响因子：
1.7
作者：
Nonacs, R;Cohen, LS
通讯作者：
Cohen, LS
DOI：
10.1002/bdrb.20099
发表时间：
2007-02-01
影响因子：
--
作者：
Berard, Anick;Ramos, Elodie;Oraichi, Driss
通讯作者：
Oraichi, Driss