Head-to-Head Study of Developmental Neurotoxicity and Resultant Phenotype in Rats: α-Hexabromocyclododecane versus Valproic Acid, a Recognized Model of Reference for Autism Spectrum Disorders

Chloé Morel, Armelle Christophe, Katy Maguin-Gaté, Justine Paoli, Jonathan David Turner, Henri Schroeder, Nathalie Grova*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Evidence is now growing that exposure to environmental pollutants during the critical early-life period of brain development may contribute to the emergence of Autism Spectrum Disorders (ASD). This study seeks to compare the developmental neurotoxicity of the α-isomer of hexabromocyclododecane (α-HBCDD), a persistent brominated flame retardant, to the valproic acid (VPA) model of ASD in rodents. Pregnant Wistar rats were divided into three groups: control, α-HBCDD (100 ng/kg/day p.o., GD0-PND21) and VPA (600 mg/kg i.p., GD12). Male offspring were tested for their neuromotor development from PND2-21. At PND21, brain functionality was assessed by measuring cytochrome oxidase activity (CO). Modifications in neuroglia and synaptic plasticity were evaluated in the cortex. Similar subtle behavioural changes related to neuromotor maturation and noise reaction were observed in both treated groups. At PND21, a reduction in CO activity was measured in the VPA group only, in specific areas including auditory nuclei, visual cortex, cingulate and frontal cortices. At the same age, α-HBCDD pointed out significant overexpression of cortical markers of synaptic plasticity while both treated groups showed a significant under expression of astrocyte proteins (S100-β and GFAP). Early-life exposure to a low dose of α-HBCDD may trigger neurobehavioural alterations in line with ASD.

Original languageEnglish
Article number180
JournalToxics
Volume10
Issue number4
DOIs
Publication statusPublished - 6 Apr 2022

Keywords

  • Autism Spectrum Disorders
  • brain functionality
  • early life exposure
  • neuroglia
  • neuromotor maturation
  • noise reaction
  • rat
  • synaptic plasticity
  • α-HBCDD

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