Prenatal exposure to benzo(a)pyrene impairs later-life cortical neuronal function

Monique M. McCallister, Mark Maguire, Aramandla Ramesh, Qiao Aimin, Sheng Liu, Habibeh Khoshbouei, Michael Aschner, Ford F. Ebner, Darryl B. Hood

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Abstract

Prenatal exposure to environmental contaminants, such as benzo(a)pyrene [B(a)P] has been shown to impair brain development. The overarching hypothesis of our work is that glutamate receptor subunit expression is crucial for cortical evoked responses and that prenatal B(a)P exposure modulates the temporal developmental expression of glutamatergic receptor subunits in the somatosensory cortex. To characterize prenatal B(a)P exposure on the development of cortical function, pregnant Long Evans rats were exposed to low-level B(a)P (300 μg/kg BW) by oral gavage on gestational days 14-17. At this exposure dose, there was no significant effect of B(a)P on (1) the number of pups born per litter, (2) the pre-weaning growth curves and (3) initial and final brain to body weight ratios. Control and B(a)P-exposed offspring were profiled for B(a)P metabolites in plasma and whole brain during the pre-weaning period. No detectable levels of metabolites were found in the control offspring. However, a time-dependent decrease in total metabolite concentration was observed in B(a)P-exposed offspring. On PND100-120, cerebrocortical mRNA expression was determined for the glutamatergic NMDA receptor subunit (NR2B) in control and B(a)P-exposed offspring. Neural activity was also recorded from neurons in primary somatic sensory (barrel) cortex. Semiquantitative PCR from B(a)P-exposed offspring revealed a significant 50% reduction in NR2B mRNA expression in B(a)P-exposed offspring relative to controls. Recordings from B(a)P-exposed offspring revealed that N-methyl-d-aspartate (NMDA) receptor-dependent neuronal activity in barrel cortex evoked by whisker stimulation was also significantly reduced (70%) as compared to controls. Analysis showed that the greatest deficit in cortical neuronal responses occurred in the shorter latency epochs from 5 to 20 ms post-stimulus. The results suggest that in utero exposure to benzo(a)pyrene results in diminished mRNA expression of the NMDA NR2B receptor subunit to result in late life deficits in cortical neuronal activity in the offspring. The findings from this study lead to a strong prediction that in utero exposure to benzo(a)pyrene at a time when synapses are first formed and adjusted in strength by activity in the sensory pathways will produce a strong negative effect on brain function in offspring progeny.

Original languageEnglish (US)
Pages (from-to)846-854
Number of pages9
JournalNeurotoxicology
Volume29
Issue number5
DOIs
StatePublished - Sep 1 2008
Externally publishedYes

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Keywords

  • Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
  • Bailey Scales of Infant Development (BSID-II)
  • Benzo(a)pyrene-B(a)P
  • Cortical neuronal activity and behavior
  • Developmental neurotoxicity
  • Environmental aryl hydrocarbon receptor agonists-eAhR agonist
  • Intrauterine growth restriction (IUGR)
  • N-methyl-d-aspartate (NMDA)
  • Polycyclic aromatic hydrocarbon-(PAH)
  • Small for gestational age (SGA)
  • Somatosensory cortex-S1 cortex
  • Susceptibility-exposure paradigm
  • World Trade Center (WTC)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

McCallister, M. M., Maguire, M., Ramesh, A., Aimin, Q., Liu, S., Khoshbouei, H., Aschner, M., Ebner, F. F., & Hood, D. B. (2008). Prenatal exposure to benzo(a)pyrene impairs later-life cortical neuronal function. Neurotoxicology, 29(5), 846-854. https://doi.org/10.1016/j.neuro.2008.07.008