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Critical periods for chlorpyrifos-induced developmental neurotoxicity: alterations in adenylyl cyclase signaling in adult rat brain regions after gestational or neonatal exposure.

Publication ,  Journal Article
Meyer, A; Seidler, FJ; Aldridge, JE; Tate, CA; Cousins, MM; Slotkin, TA
Published in: Environ Health Perspect
March 2004

Developmental exposure to chlorpyrifos (CPF) alters the function of a wide variety of neural systems. In the present study we evaluated the effects in adulthood of CPF exposure of rats during different developmental windows, using the adenylyl cyclase (AC) signaling cascade, which mediates the cellular responses to numerous neurotransmitters. Animals were exposed on gestational days (GD) 9-12 or 17-20 or on postnatal days (PN) 1-4 or 11-14 and assessed at PN60. In addition to basal AC activity, we evaluated the responses to direct AC stimulants (forskolin, Mn2+) and to isoproterenol, which activates signaling through ss-adrenoceptors coupled to stimulatory G-proteins. CPF exposure in any of the four periods elicited significant changes in AC signaling in a wide variety of brain regions in adulthood. In general, GD9-12 was the least sensitive stage, requiring doses above the threshold for impaired maternal weight gain, whereas effects were obtained at subtoxic doses for all other regimens. Most of the effects were heterologous, involving signaling elements downstream from the receptors, and thus shared by multiple stimulants; superimposed on this basic pattern, there were also selective alterations in receptor-mediated responses, in G-protein function, and in AC expression and subtypes. Exposures conducted at GD17-20 and later all produced sex-selective alterations. These results suggest that developmental exposure to CPF elicits long-lasting alterations in cell-signaling cascades that are shared by multiple neurotransmitter and hormonal inputs; the resultant abnormalities of synaptic communication are thus likely to occur in widespread neural circuits and their corresponding behaviors.

Duke Scholars

Published In

Environ Health Perspect

DOI

ISSN

0091-6765

Publication Date

March 2004

Volume

112

Issue

3

Start / End Page

295 / 301

Location

United States

Related Subject Headings

  • Toxicology
  • Signal Transduction
  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Male
  • Isoproterenol
  • Insecticides
 

Citation

APA
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ICMJE
MLA
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Meyer, A., Seidler, F. J., Aldridge, J. E., Tate, C. A., Cousins, M. M., & Slotkin, T. A. (2004). Critical periods for chlorpyrifos-induced developmental neurotoxicity: alterations in adenylyl cyclase signaling in adult rat brain regions after gestational or neonatal exposure. Environ Health Perspect, 112(3), 295–301. https://doi.org/10.1289/ehp.6755
Meyer, Armando, Frederic J. Seidler, Justin E. Aldridge, Charlotte A. Tate, Mandy M. Cousins, and Theodore A. Slotkin. “Critical periods for chlorpyrifos-induced developmental neurotoxicity: alterations in adenylyl cyclase signaling in adult rat brain regions after gestational or neonatal exposure.Environ Health Perspect 112, no. 3 (March 2004): 295–301. https://doi.org/10.1289/ehp.6755.
Meyer, Armando, et al. “Critical periods for chlorpyrifos-induced developmental neurotoxicity: alterations in adenylyl cyclase signaling in adult rat brain regions after gestational or neonatal exposure.Environ Health Perspect, vol. 112, no. 3, Mar. 2004, pp. 295–301. Pubmed, doi:10.1289/ehp.6755.

Published In

Environ Health Perspect

DOI

ISSN

0091-6765

Publication Date

March 2004

Volume

112

Issue

3

Start / End Page

295 / 301

Location

United States

Related Subject Headings

  • Toxicology
  • Signal Transduction
  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Male
  • Isoproterenol
  • Insecticides