Cardiac Outcomes after Perinatal Sertraline Exposure in Mice

Sarah E. Haskell; Cecilia Lo; Mitchell E. Kent; Timothy M. Eggleston; Kenneth A. Volk; Benjamin E. Reinking; Robert D. Roghair

doi:10.1097/FJC.0000000000000501

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Cardiac Outcomes after Perinatal Sertraline Exposure in Mice

Journal article

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Peer reviewed

Cardiac Outcomes after Perinatal Sertraline Exposure in Mice

Sarah E. Haskell, Cecilia Lo, Mitchell E. Kent, Timothy M. Eggleston, Kenneth A. Volk, Benjamin E. Reinking and Robert D. Roghair

Journal of cardiovascular pharmacology, Vol.70(2), pp.119-127

08/01/2017

DOI: 10.1097/FJC.0000000000000501

PMCID: PMC5538912

PMID: 28459713

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https://www.ncbi.nlm.nih.gov/pmc/articles/5538912View

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Abstract

Selective serotonin reuptake inhibitors are prescribed to 6–10% of pregnant women in the United States. Using an intrauterine plus neonatal exposure model to represent exposure throughout human pregnancy, we hypothesized sertraline exposure would impact intracardiac serotonin signaling and lead to small left heart syndrome in the absence of maternal psychopathology. C57BL/6 adult female mice received sertraline (5 mg/kg/d IP) or saline throughout pregnancy to time of delivery. Pups maintained exposure on postnatal days 1–14 to encompass the developmental window analogous to human gestation. Sertraline-exposed mice had increased cardiac hydroxyproline content, decreased 5-HT 2B receptor mRNA levels, and increased 5-HT 2A receptor and serotonin transporter mRNA levels on postnatal day 21 (p<0.05). These changes were associated with diminished exercise capacity at 6 weeks (p<0.05) and decreased adult shortening fraction and stroke volume at 5 months of age. Isolated cardiomyocytes from neonatal sertraline-exposed mice had significantly decreased proliferation, cross-sectional area and phosphorylation of Akt (p<0.05 versus neonatal control mice). Perinatal sertraline exposure alters neonatal cardiac development and produces long standing changes in adult cardiac function and exercise capacity. Further studies are needed to assess if similar findings are present in the growing population that has been exposed to SSRIs during development.

cardiac development

cardiac function

selective serotonin reuptake inhibitors

serotonin receptors

Details

Title: Subtitle: Cardiac Outcomes after Perinatal Sertraline Exposure in Mice
Creators: Sarah E. Haskell - University of Iowa
Cecilia Lo - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242
Mitchell E. Kent - University of Iowa
Timothy M. Eggleston - University of Iowa
Kenneth A. Volk - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242
Benjamin E. Reinking - University of Iowa
Robert D. Roghair - University of Iowa
Resource Type: Journal article
Publication Details: Journal of cardiovascular pharmacology, Vol.70(2), pp.119-127
DOI: 10.1097/FJC.0000000000000501
PMID: 28459713
PMCID: PMC5538912
NLM abbreviation: J Cardiovasc Pharmacol
ISSN: 0160-2446
eISSN: 1533-4023
Language: English
Date published: 08/01/2017
Academic Unit: Critical Care; Cardiology; Stead Family Department of Pediatrics; Neonatology; Ophthalmology and Visual Sciences
Record Identifier: 9984353829902771

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