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Developmental neurotoxicity resulting from pharmacotherapy of preterm labor, modeled in vitro: Terbutaline and dexamethasone, separately and together.

Publication ,  Journal Article
Slotkin, TA; Skavicus, S; Seidler, FJ
Published in: Toxicology
May 1, 2018

Terbutaline and dexamethasone are used in the management of preterm labor, often for durations of treatment exceeding those recommended, and both have been implicated in increased risk of neurodevelopmental disorders. We used a variety of cell models to establish the critical stages at which neurodifferentiation is vulnerable to these agents and to determine whether combined exposures produce a worsened outcome. Terbutaline selectively promoted the initial emergence of glia from embryonic neural stem cells (NSCs). The target for terbutaline shifted with developmental stage: at later developmental stages modeled with C6 and PC12 cells, terbutaline had little effect on glial differentiation (C6 cells) but impaired the differentiation of neuronotypic PC12 cells into neurotransmitter phenotypes. In contrast to the specificity shown by terbutaline, dexamethasone affected both neuronal and glial differentiation at all stages, impairing the emergence of both cell types in NSCs but with a much greater impairment for glia. At later stages, dexamethasone promoted glial cell differentiation (C6 cells), while shifting neuronal cell differentiation so as to distort the balance of neurotransmitter phenotypes (PC12 cells). Finally, terbutaline and dexamethasone interacted synergistically at the level of late stage glial cell differentiation, with dexamethasone boosting the ability of terbutaline to enhance indices of glial cell growth and neurite formation while producing further decrements in glial cell numbers. Our results support the conclusion that terbutaline and dexamethasone are directly-acting neuroteratogens, and further indicate the potential for their combined use in preterm labor to worsen neurodevelopmental outcomes.

Duke Scholars

Published In

Toxicology

DOI

EISSN

1879-3185

Publication Date

May 1, 2018

Volume

400-401

Start / End Page

57 / 64

Location

Ireland

Related Subject Headings

  • Toxicology
  • Terbutaline
  • Rats
  • Pregnancy
  • PC12 Cells
  • Obstetric Labor, Premature
  • Neurotoxicity Syndromes
  • Neurons
  • Neuroglia
  • Glucocorticoids
 

Citation

APA
Chicago
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MLA
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Slotkin, T. A., Skavicus, S., & Seidler, F. J. (2018). Developmental neurotoxicity resulting from pharmacotherapy of preterm labor, modeled in vitro: Terbutaline and dexamethasone, separately and together. Toxicology, 400401, 57–64. https://doi.org/10.1016/j.tox.2018.03.001
Slotkin, Theodore A., Samantha Skavicus, and Frederic J. Seidler. “Developmental neurotoxicity resulting from pharmacotherapy of preterm labor, modeled in vitro: Terbutaline and dexamethasone, separately and together.Toxicology 400–401 (May 1, 2018): 57–64. https://doi.org/10.1016/j.tox.2018.03.001.
Slotkin, Theodore A., et al. “Developmental neurotoxicity resulting from pharmacotherapy of preterm labor, modeled in vitro: Terbutaline and dexamethasone, separately and together.Toxicology, vol. 400–401, May 2018, pp. 57–64. Pubmed, doi:10.1016/j.tox.2018.03.001.
Journal cover image

Published In

Toxicology

DOI

EISSN

1879-3185

Publication Date

May 1, 2018

Volume

400-401

Start / End Page

57 / 64

Location

Ireland

Related Subject Headings

  • Toxicology
  • Terbutaline
  • Rats
  • Pregnancy
  • PC12 Cells
  • Obstetric Labor, Premature
  • Neurotoxicity Syndromes
  • Neurons
  • Neuroglia
  • Glucocorticoids