King Jennifer R, Velasquez Juan C, Torii Masaaki, Bonnin Alexandre
Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Keck School of Medicine, University of Southern California , Los Angeles, California 90089, United States.
Zilkha Neurogenetic Institute and Department of Cell and Neurobiology, Keck School of Medicine of University of Southern California , Los Angeles, California 90089, United States.
ACS Chem Neurosci. 2017 May 17;8(5):1019-1025. doi: 10.1021/acschemneuro.6b00339. Epub 2017 Jan 13.
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.
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风险增加有关。在成人大脑中，SSRI疗法调节p11（s100a10）表达并改变神经发生。蛋白质p11通过5-HT1B/D受体间接调节5-羟色胺信号传导。在胎儿大脑中，通过这些受体的信号传导调节轴突回路形成。我们确定了p11是否在胎鼠大脑中表达，以及母体暴露于SSRI是否会影响胎儿p11表达和神经发生。从妊娠第8天到第17天，给怀孕小鼠施用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，子宫内±西酞普兰暴露后胎儿丘脑中p11蛋白表达显著降低，并且特定胎儿脑区的神经发生显著减少。这些发现揭示了由于母体暴露于SSRI，胎儿大脑中p11表达的差异调节和神经发生的改变。
