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Serotonergic systems targeted by developmental exposure to chlorpyrifos: effects during different critical periods.

Publication ,  Journal Article
Aldridge, JE; Seidler, FJ; Meyer, A; Thillai, I; Slotkin, TA
Published in: Environ Health Perspect
November 2003

During brain development, serotonin (5HT) provides essential neurotrophic signals. In the present study, we evaluated whether the developmental neurotoxicity of chlorpyrifos (CPF) involves effects on 5HT signaling, as a potential mechanism underlying noncholinergic neuroteratogenic events. We evaluated four different treatment windows ranging from the neural tube stage [gestational days (GD) 9-12] and the late gestational period (GD17-20) through postnatal phases of terminal neuronal differentiation and synaptogenesis [postnatal days (PN) 1-4, PN11-14]. Exposure to CPF on GD9-12 elicited initial suppression, immediately followed by rebound elevation, of 5HT1A and 5HT2 receptors as well as the 5HT transporter, all at doses below the threshold for cholinergic hyperstimulation and the resultant systemic toxicity. In contrast, with GD17-20 exposure, the initial effect was augmentation of all three components by low doses of CPF. Sensitivity of these effects declined substantially when exposure was shifted to the postnatal period. We also identified major alterations in 5HT-mediated responses, assessed for the adenylyl cyclase signaling cascade. Although GD9-12 exposure had only minor effects, treatment on GD17-20 elicited supersensitivity to both stimulatory and inhibitory responses mediated by 5HT. Our results indicate that CPF affects 5HT receptors, the presynaptic 5HT transporter, and 5HT-mediated signal transduction during a discrete critical gestational window. These effects are likely to contribute to the noncholinergic component of CPF's developmental neurotoxicity.

Duke Scholars

Published In

Environ Health Perspect

DOI

ISSN

0091-6765

Publication Date

November 2003

Volume

111

Issue

14

Start / End Page

1736 / 1743

Location

United States

Related Subject Headings

  • Toxicology
  • Signal Transduction
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Receptors, Serotonin
  • Rats, Sprague-Dawley
  • Rats
  • Pregnancy
  • Nerve Tissue Proteins
  • Membrane Transport Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Aldridge, J. E., Seidler, F. J., Meyer, A., Thillai, I., & Slotkin, T. A. (2003). Serotonergic systems targeted by developmental exposure to chlorpyrifos: effects during different critical periods. Environ Health Perspect, 111(14), 1736–1743. https://doi.org/10.1289/ehp.6489
Aldridge, Justin E., Frederic J. Seidler, Armando Meyer, Indira Thillai, and Theodore A. Slotkin. “Serotonergic systems targeted by developmental exposure to chlorpyrifos: effects during different critical periods.Environ Health Perspect 111, no. 14 (November 2003): 1736–43. https://doi.org/10.1289/ehp.6489.
Aldridge JE, Seidler FJ, Meyer A, Thillai I, Slotkin TA. Serotonergic systems targeted by developmental exposure to chlorpyrifos: effects during different critical periods. Environ Health Perspect. 2003 Nov;111(14):1736–43.
Aldridge, Justin E., et al. “Serotonergic systems targeted by developmental exposure to chlorpyrifos: effects during different critical periods.Environ Health Perspect, vol. 111, no. 14, Nov. 2003, pp. 1736–43. Pubmed, doi:10.1289/ehp.6489.
Aldridge JE, Seidler FJ, Meyer A, Thillai I, Slotkin TA. Serotonergic systems targeted by developmental exposure to chlorpyrifos: effects during different critical periods. Environ Health Perspect. 2003 Nov;111(14):1736–1743.

Published In

Environ Health Perspect

DOI

ISSN

0091-6765

Publication Date

November 2003

Volume

111

Issue

14

Start / End Page

1736 / 1743

Location

United States

Related Subject Headings

  • Toxicology
  • Signal Transduction
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Receptors, Serotonin
  • Rats, Sprague-Dawley
  • Rats
  • Pregnancy
  • Nerve Tissue Proteins
  • Membrane Transport Proteins