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Chlorpyrifos exposure during neurulation: cholinergic synaptic dysfunction and cellular alterations in brain regions at adolescence and adulthood.

Publication ,  Journal Article
Qiao, D; Seidler, FJ; Abreu-Villaça, Y; Tate, CA; Cousins, MM; Slotkin, TA
Published in: Brain Res Dev Brain Res
January 31, 2004

The developmental neurotoxicity of chlorpyrifos (CPF) involves multiple mechanisms, thus rendering the immature brain susceptible to adverse effects over a wide window of vulnerability. Earlier work indicated that CPF exposure at the neural tube stage elicits apoptosis and disrupts mitotic patterns in the brain primordium but that rapid recovery ensues before birth. In the current study, we assessed whether defects in cholinergic synaptic activity emerge later in development. CPF was given to pregnant rats on gestational days 9-12, using regimens devoid of overt maternal or fetal toxicity. We then examined subsequent development of acetylcholine systems and compared the effects to those on general biomarkers of cell development. Choline acetyltransferase (ChAT), a constitutive marker for cholinergic nerve terminals, was increased in the hippocampus and striatum in adolescence and adulthood. In contrast, hemicholinium-3 (HC-3) binding to the presynaptic choline transporter, an index of nerve impulse activity, was markedly subnormal. Furthermore, m2-muscarinic cholinergic receptor binding was significantly reduced, instead of showing the expected compensatory upregulation for reduced neural input. CPF also elicited delayed-onset alterations in biomarkers of cell packing density, cell number, cell size and neuritic projections, involving brain regions both with and without reductions in indices of cholinergic activity. In combination with earlier results, the current findings indicate that the developing brain, and especially the hippocampus, is adversely affected by CPF regardless of whether exposure occurs early or late in brain development, and that defects emerge in adolescence or adulthood even in situations where normative values are initially restored in the immediate post-exposure period.

Duke Scholars

Published In

Brain Res Dev Brain Res

DOI

ISSN

0165-3806

Publication Date

January 31, 2004

Volume

148

Issue

1

Start / End Page

43 / 52

Location

Netherlands

Related Subject Headings

  • Synapses
  • Sex Factors
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Pirenzepine
  • Neurotransmitter Uptake Inhibitors
  • Neurons
 

Citation

APA
Chicago
ICMJE
MLA
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Qiao, D., Seidler, F. J., Abreu-Villaça, Y., Tate, C. A., Cousins, M. M., & Slotkin, T. A. (2004). Chlorpyrifos exposure during neurulation: cholinergic synaptic dysfunction and cellular alterations in brain regions at adolescence and adulthood. Brain Res Dev Brain Res, 148(1), 43–52. https://doi.org/10.1016/j.devbrainres.2003.10.004
Qiao, Dan, Frederic J. Seidler, Yael Abreu-Villaça, Charlotte A. Tate, Mandy M. Cousins, and Theodore A. Slotkin. “Chlorpyrifos exposure during neurulation: cholinergic synaptic dysfunction and cellular alterations in brain regions at adolescence and adulthood.Brain Res Dev Brain Res 148, no. 1 (January 31, 2004): 43–52. https://doi.org/10.1016/j.devbrainres.2003.10.004.
Qiao D, Seidler FJ, Abreu-Villaça Y, Tate CA, Cousins MM, Slotkin TA. Chlorpyrifos exposure during neurulation: cholinergic synaptic dysfunction and cellular alterations in brain regions at adolescence and adulthood. Brain Res Dev Brain Res. 2004 Jan 31;148(1):43–52.
Qiao, Dan, et al. “Chlorpyrifos exposure during neurulation: cholinergic synaptic dysfunction and cellular alterations in brain regions at adolescence and adulthood.Brain Res Dev Brain Res, vol. 148, no. 1, Jan. 2004, pp. 43–52. Pubmed, doi:10.1016/j.devbrainres.2003.10.004.
Qiao D, Seidler FJ, Abreu-Villaça Y, Tate CA, Cousins MM, Slotkin TA. Chlorpyrifos exposure during neurulation: cholinergic synaptic dysfunction and cellular alterations in brain regions at adolescence and adulthood. Brain Res Dev Brain Res. 2004 Jan 31;148(1):43–52.
Journal cover image

Published In

Brain Res Dev Brain Res

DOI

ISSN

0165-3806

Publication Date

January 31, 2004

Volume

148

Issue

1

Start / End Page

43 / 52

Location

Netherlands

Related Subject Headings

  • Synapses
  • Sex Factors
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Pirenzepine
  • Neurotransmitter Uptake Inhibitors
  • Neurons