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Quantitative morphological assessment reveals neuronal and glial deficits in hippocampus after a brief subtoxic exposure to chlorpyrifos in neonatal rats.

Publication ,  Journal Article
Roy, TS; Sharma, V; Seidler, FJ; Slotkin, TA
Published in: Brain Res Dev Brain Res
March 22, 2005

Neurochemical and behavioral studies indicate that the widely used organophosphorus insecticide, chlorpyrifos (CPF), evokes neurobehavioral teratogenicity with a wide window of vulnerability, ranging from embryonic life through postnatal development. Few studies have detailed morphological damage that corresponds to the operational deficits. We administered 5 mg/kg of CPF sc daily on postnatal days (PN) 11-14, a regimen that is devoid of systemic toxicity, but that elicits long-term cognitive impairment and disruption of cholinergic, catecholaminergic, and serotonergic synaptic function. On PN15 and 20, we conducted quantitative morphologic examinations of neurons and glia in CA1, CA3, and dentate gyrus regions of the hippocampus. Although hippocampal morphology after CPF exposure was normal on gross observation, morphometric analysis revealed a significant overall reduction in the total number of neurons and glia. Superimposed on this basic effect, CPF elicited a delayed-onset increase in the neuron/glia ratio that emerged by PN20, connoting selective gliotoxicity. The alterations in cell numbers were accompanied by significant perikaryal swelling and by enhanced development of astrocytic processes. Layer thickness also showed delayed-onset effects of CPF, with thinning of the CA1 and CA3 layers and enlargement of the dentate gyrus. Our results indicate that there are subtle morphological changes in the juvenile rat brain after neonatal CPF exposure that are detectable only with quantitative analysis and that correlate with regional and cell-specific targets identified earlier in neurochemical studies. The simultaneous targeting of neurons and glia by CPF is likely to play an important role in its developmental neurotoxicant effects.

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Published In

Brain Res Dev Brain Res

DOI

ISSN

0165-3806

Publication Date

March 22, 2005

Volume

155

Issue

1

Start / End Page

71 / 80

Location

Netherlands

Related Subject Headings

  • Synaptic Transmission
  • Sex Factors
  • Rats, Sprague-Dawley
  • Rats
  • Neurotoxins
  • Neurons
  • Neurology & Neurosurgery
  • Neuroglia
  • Nerve Degeneration
  • Male
 

Citation

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Roy, T. S., Sharma, V., Seidler, F. J., & Slotkin, T. A. (2005). Quantitative morphological assessment reveals neuronal and glial deficits in hippocampus after a brief subtoxic exposure to chlorpyrifos in neonatal rats. Brain Res Dev Brain Res, 155(1), 71–80. https://doi.org/10.1016/j.devbrainres.2004.12.004
Roy, Tara Sankar, Vikram Sharma, Frederic J. Seidler, and Theodore A. Slotkin. “Quantitative morphological assessment reveals neuronal and glial deficits in hippocampus after a brief subtoxic exposure to chlorpyrifos in neonatal rats.Brain Res Dev Brain Res 155, no. 1 (March 22, 2005): 71–80. https://doi.org/10.1016/j.devbrainres.2004.12.004.
Roy, Tara Sankar, et al. “Quantitative morphological assessment reveals neuronal and glial deficits in hippocampus after a brief subtoxic exposure to chlorpyrifos in neonatal rats.Brain Res Dev Brain Res, vol. 155, no. 1, Mar. 2005, pp. 71–80. Pubmed, doi:10.1016/j.devbrainres.2004.12.004.
Journal cover image

Published In

Brain Res Dev Brain Res

DOI

ISSN

0165-3806

Publication Date

March 22, 2005

Volume

155

Issue

1

Start / End Page

71 / 80

Location

Netherlands

Related Subject Headings

  • Synaptic Transmission
  • Sex Factors
  • Rats, Sprague-Dawley
  • Rats
  • Neurotoxins
  • Neurons
  • Neurology & Neurosurgery
  • Neuroglia
  • Nerve Degeneration
  • Male