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Prenatal dexamethasone, as used in preterm labor, worsens the impact of postnatal chlorpyrifos exposure on serotonergic pathways.

Publication ,  Journal Article
Slotkin, TA; Card, J; Seidler, FJ
Published in: Brain Res Bull
January 2014

This study explores how glucocorticoids sensitize the developing brain to the organophosphate pesticide, chlorpyrifos. Pregnant rats received a standard therapeutic dose (0.2mg/kg) of dexamethasone on gestational days 17-19; pups were given subtoxic doses of chlorpyrifos on postnatal days 1-4 (1mg/kg, <10% cholinesterase inhibition). We evaluated serotonin (5HT) synaptic function from postnatal day 30 to day 150, assessing the expression of 5HT receptors and the 5HT transporter, along with 5HT turnover (index of presynaptic impulse activity) in brain regions encompassing all the 5HT projections and cell bodies. These parameters are known targets for neurodevelopmental effects of dexamethasone and chlorpyrifos individually. In males, chlorpyrifos evoked overall elevations in the expression of 5HT synaptic proteins, with a progressive increase from adolescence to adulthood; this effect was attenuated by prenatal dexamethasone treatment. The chlorpyrifos-induced upregulation was preceded by deficits in 5HT turnover, indicating that the receptor upregulation was an adaptive response to deficient presynaptic activity. Turnover deficiencies were magnified by dexamethasone pretreatment, worsening the functional impairment caused by chlorpyrifos. In females, chlorpyrifos-induced receptor changes reflected relative sparing of adverse effects compared to males. Nevertheless, prenatal dexamethasone still worsened the 5HT turnover deficits and reduced 5HT receptor expression in females, demonstrating the same adverse interaction. Glucocorticoids are used in 10% of U.S. pregnancies, and are also elevated in maternal stress; accordingly, our results indicate that this group represents a large subpopulation that may have heightened vulnerability to developmental neurotoxicants such as the organophosphates.

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Published In

Brain Res Bull

DOI

EISSN

1873-2747

Publication Date

January 2014

Volume

100

Start / End Page

44 / 54

Location

United States

Related Subject Headings

  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Receptors, Serotonin
  • Rats, Sprague-Dawley
  • Rats
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Obstetric Labor, Premature
  • Neurology & Neurosurgery
  • Male
 

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Slotkin, T. A., Card, J., & Seidler, F. J. (2014). Prenatal dexamethasone, as used in preterm labor, worsens the impact of postnatal chlorpyrifos exposure on serotonergic pathways. Brain Res Bull, 100, 44–54. https://doi.org/10.1016/j.brainresbull.2013.10.014
Slotkin, Theodore A., Jennifer Card, and Frederic J. Seidler. “Prenatal dexamethasone, as used in preterm labor, worsens the impact of postnatal chlorpyrifos exposure on serotonergic pathways.Brain Res Bull 100 (January 2014): 44–54. https://doi.org/10.1016/j.brainresbull.2013.10.014.
Slotkin, Theodore A., et al. “Prenatal dexamethasone, as used in preterm labor, worsens the impact of postnatal chlorpyrifos exposure on serotonergic pathways.Brain Res Bull, vol. 100, Jan. 2014, pp. 44–54. Pubmed, doi:10.1016/j.brainresbull.2013.10.014.
Journal cover image

Published In

Brain Res Bull

DOI

EISSN

1873-2747

Publication Date

January 2014

Volume

100

Start / End Page

44 / 54

Location

United States

Related Subject Headings

  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Receptors, Serotonin
  • Rats, Sprague-Dawley
  • Rats
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Obstetric Labor, Premature
  • Neurology & Neurosurgery
  • Male