TY - JOUR
T1 - Head-to-Head Study of Developmental Neurotoxicity and Resultant Phenotype in Rats
T2 - α-Hexabromocyclododecane versus Valproic Acid, a Recognized Model of Reference for Autism Spectrum Disorders
AU - Morel, Chloé
AU - Christophe, Armelle
AU - Maguin-Gaté, Katy
AU - Paoli, Justine
AU - Turner, Jonathan David
AU - Schroeder, Henri
AU - Grova, Nathalie
N1 - Funding Information:
Funding: This research was funded by the A2F young research grant—Lorraine University. We acknowledge the support of the “Ministère de l’Enseignement supérieur et de la Recherche” in France. This study was partly funded by the Fonds National de Recherche Luxembourg: FNR-CORE (C16/BM/11342695 “MetCOEPs”) and FNR INTER (INTER/ANR/16/11568350 “MADAM”). JDT is a management committee member of the EU funded COST action CA18211.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/4/6
Y1 - 2022/4/6
N2 - 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.
AB - 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.
KW - Autism Spectrum Disorders
KW - brain functionality
KW - early life exposure
KW - neuroglia
KW - neuromotor maturation
KW - noise reaction
KW - rat
KW - synaptic plasticity
KW - α-HBCDD
UR - http://www.scopus.com/inward/record.url?scp=85128712942&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/35448441
U2 - 10.3390/toxics10040180
DO - 10.3390/toxics10040180
M3 - Article
C2 - 35448441
AN - SCOPUS:85128712942
VL - 10
JO - Toxics
JF - Toxics
IS - 4
M1 - 180
ER -