In Utero Exposure to Citalopram Mitigates Maternal Stress Effects on Fetal Brain Development.
In Utero Exposure to Citalopram Mitigates Maternal Stress Effects on Fetal Brain Development.
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在子宫内接触西酞普兰可减轻母体压力对胎儿大脑发育的影响。
DOI：
10.1021/acschemneuro.9b00180
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发表时间：
2019
影响因子：
5
通讯作者：
Bonnin,Alexandre
中科院分区：
文献类型：
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作者：
Velasquez,JuanC;Zhao,Qiuying;Chan,Yen;Galindo,LigiaCM;Simasotchi,Christelle;Wu,Dan;Hou,Zhipeng;Herod,SkylaM;Oberlander,TimF;Gil,Sophie;Fournier,Thierry;Burd,Irina;Andrews,AnneM;Bonnin,Alexandre
人类流行病学和动物模型研究表明，妊娠期间单独暴露于压力或选择性再摄取抑制剂（SSRI）抗抑郁药会增加后代神经发育障碍的风险。然而，关于母体压力和SSRIs对子宫内大脑发育的综合影响知之甚少。我们发现，胎盘对人类和小鼠常用的SSRI（±）-西酞普兰（CIT）具有高度渗透性，使胎儿大脑快速暴露于这种药物。我们研究了母体慢性不可预测的应激对小鼠的影响，从胚胎第8天（E）到E17，有或没有母体口服CIT。我们利用磁共振成像评估胎儿大脑发育，并量化了多巴胺能神经、丘脑皮质和皮质发育的变化。然而，5-羟色胺组织含量在胎儿前脑增加与母亲的压力，这种增加被逆转的maternal CIT.In子宫暴露于压力增加了深层神经元的数量在特定的皮质区域，而CIT增加整体细胞数量没有改变层特定的神经元的比例，以抵消压力对深层皮质发育的影响。这些发现表明，压力和SSRI子宫内分泌系统差异性地影响了降钙素依赖的胎儿神经发育，因此CIT逆转了母体妊娠压力对后代大脑发育的关键影响。
Human epidemiological and animal-model studies suggest that separate exposure to stress or serotonin-selective reuptake inhibitor (SSRI) antidepressants during pregnancy increases risks for neurodevelopmental disorders in offspring. Yet, little is known about the combined effects of maternal stress and SSRIs with regard to brain developmentin utero. We found that the placenta is highly permeable to the commonly prescribed SSRI (±)-citalopram (CIT) in humans and mice, allowing rapid exposure of the fetal brain to this drug. We investigated the effects of maternal chronic unpredictable stress in mice with or without maternal oral administration of CIT from embryonic day (E)8 to E17. We assessed fetal brain development using magnetic resonance imaging and quantified changes in serotonergic, thalamocortical, and cortical development.In uteroexposure to maternal stress did not affect overall fetal brain growth. However, serotonin tissue content in the fetal forebrain was increased in association with maternal stress; this increase was reversed by maternal CIT.In uteroexposure to stress increased the numbers of deep-layer neurons in specific cortical regions, whereas CIT increased overall cell numbers without changing the proportions of layer-specific neurons to offset the effects of stress on deep-layer cortical development. These findings suggest that stress and SSRI exposurein uterodifferentially impact serotonin-dependent fetal neurodevelopment such that CIT reverses key effects of maternal gestational stress on offspring brain development.