Electro-behavioral phenotype and cell injury following exposure to paraoxon-ethyl in mice: Effect of the genetic background

Chem Biol Interact. 2018 Jun 25:290:119-125. doi: 10.1016/j.cbi.2018.05.009. Epub 2018 May 22.

Abstract

Organophosphorus compounds (OP) are irreversible inhibitors of both central and peripheral cholinesterases (ChE). They still represent a major health issue in some countries as well as a terrorist and military threat. In order to design appropriate medical counter-measures, a better understanding of the pathophysiology of the poisoning is needed. Little to nothing is known regarding the impact of the genetic background on OP-induced seizures and seizure-related cell injury. Using two different mouse strains, Swiss and C57BL/6J, exposed to a convulsing dose of the OP pesticide paraoxon-ethyl (POX), our study focused on seizure susceptibility, especially the occurrence of SE and related mortality. We also evaluated the initial neuropathological response and SE-induced cell injury. Following the administration of 2.4 mg/kg POX, more Swiss mice experienced SE than C57BL/6J (55.6% versus 17.2%) but the duration of their SE, based on EEG recordings, was shorter (64.3 ± 19.5 min versus 180.8 ± 36.8 min). No significant difference was observed between strains regarding mortality (33% versus 14%). In both strains limited cell injury was observed in the medial temporal cortex, the dentate gyrus and the CA3 field without inter-strain differences (Fluorojade C-positive cells/mm2). Conversely, only C57BL/6J mice showed cell injury in the CA1 field. There was no obvious correlation between the number of Fluorojade C-positive cells and the duration of the EEG discharges. Our work suggests some differences between Swiss and C57BL/6J mice and lay ground to further studies on the impact of strains in the development of central nervous system toxicity of OP.

Keywords: C57BL/6J and Swiss mice; Cell injury; Electro-behavioral phenotype; Genetic background; Organophosphorus pesticide; Status epilepticus.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Behavior, Animal / drug effects*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / metabolism
  • Dentate Gyrus / pathology
  • Electroencephalography
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Agents / toxicity*
  • Paraoxon / analogs & derivatives*
  • Paraoxon / toxicity
  • Temporal Lobe / drug effects
  • Temporal Lobe / metabolism
  • Temporal Lobe / pathology

Substances

  • Cytokines
  • Nerve Agents
  • ethylparaoxon
  • Paraoxon