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ACS Chem Neurosci. 2017 May 17;8(5):1019-1025. doi: 10.1021/acschemneuro.6b00339. Epub 2017 Jan 13.

Effect of Maternal ±Citalopram Exposure on P11 Expression and Neurogenesis in the Mouse Fetal Brain.

Author information

1
Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Keck School of Medicine, University of Southern California , Los Angeles, California 90089, United States.
2
Zilkha Neurogenetic Institute and Department of Cell and Neurobiology, Keck School of Medicine of University of Southern California , Los Angeles, California 90089, United States.
3
Center for Neuroscience Research, Children's National Medical Center , Washington, D.C. 20010, United States.
4
Department of Pediatrics, Pharmacology and Physiology, The George Washington University , Washington, D.C. 20052, United States.

Abstract

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.

KEYWORDS:

P11; SSRI; citalopram; fetal brain; neurogenesis; pregnancy; serotonin

PMID:
28076682
PMCID:
PMC5453513
DOI:
10.1021/acschemneuro.6b00339
[Indexed for MEDLINE]
Free PMC Article

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