Effect of Maternal ±Citalopram Exposure on P11 Expression and Neurogenesis in the Mouse Fetal Brain.
Effect of Maternal ±Citalopram Exposure on P11 Expression and Neurogenesis in the Mouse Fetal Brain.
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DOI：
10.1021/acschemneuro.6b00339
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发表时间：
2017-05-17
影响因子：
5
通讯作者：
Bonnin A
中科院分区：
文献类型：
--
作者：
King JR;Velasquez JC;Torii M;Bonnin A
胎儿暴露于选择性5-羟色胺再摄取抑制剂（SSRI）与不良神经发育结局的风险增加有关。在成人大脑中，SSRI治疗调节p11（s100 a10）表达并改变神经发生。p11蛋白通过5-HT 1B/D受体间接调节5-HT信号传导。在胎儿大脑中，通过这些受体的信号调节轴突回路的形成。我们确定了p11是否在胎鼠脑中表达，以及母体SSRI暴露是否影响胎鼠p11表达和神经发生。从妊娠第8天至第17天向妊娠小鼠施用SSRI ±西酞普兰。结果表明，p11在胎儿丘脑神经元和丘脑皮质轴突中表达。此外，与未处理的对照组相比，宫内±西酞普兰暴露后，胎儿丘脑中的p11蛋白表达显著降低，特定胎儿脑区域的神经发生显著降低。这些研究结果揭示了差异调节p11的表达和改变神经发生在胎儿大脑作为一个结果母体SSRI曝光。
Fetal exposure to selective serotonin reuptake inhibitors (SSRI) has been associated with increased risk of adverse neurodevelopmental outcomes. In the adult brain, SSRI therapy regulates p11 (s100a10) expression and alters neurogenesis. The protein p11 indirectly regulates 5-HT signaling through 5-HT1B/D receptors. In the fetal brain, signaling through these receptors modulates axonal circuit formation. We determined whether p11 is expressed in the fetal mouse brain, and whether maternal SSRI exposure affects fetal p11 expression and neurogenesis. The SSRI ± citalopram was administered to pregnant mice from gestational day 8 to 17. Results show that p11 is expressed in fetal thalamic neurons and thalamocortical axons. Furthermore, p11 protein expression is significantly decreased in the fetal thalamus after in utero ±citalopram exposure compared to untreated controls, and neurogenesis is significantly decreased in specific fetal brain regions. These findings reveal differential regulation of p11 expression and altered neurogenesis in the fetal brain as a result of maternal SSRI exposure.