In utero exposure to citalopram mitigates maternal stress effects on fetal brain development

Juan C. Velasquez, Qiuying Zhao, Yen Chan, Ligia C.M. Galindo, Christelle Simasotchi, Dan Wu, Zhipeng Hou, Skyla M. Herod, Tim F. Oberlander, Sophie Gil, Thierry Fournier, Irina Burd, Anne M. Andrews, Alexandre Bonnin

Research output: Contribution to journalArticlepeer-review

Abstract

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 development in 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 utero exposure 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 utero exposure 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 exposure in utero differentially impact serotonin-dependent fetal neurodevelopment such that CIT reverses key effects of maternal gestational stress on offspring brain development.

Original languageEnglish (US)
Pages (from-to)3307-3317
Number of pages11
JournalACS Chemical Neuroscience
Volume10
Issue number7
DOIs
StatePublished - Jul 17 2019

Keywords

  • Serotonin
  • antidepressant
  • behavior
  • cortex
  • pregnancy
  • serotonin-selective reuptake inhibitor
  • thalamocortical axons

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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