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

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.

Auditory processing in rodent models of autism: a systematic review

“…The number and size of neurons in the MGN of Cntnap2 −/− mice has been shown to be reduced [ 140 ]. Despite increased sound-evoked activity shown by c-Fos staining, CO staining showed reduced activity in the IC, LL, and MGN in the absence of sound stimulation in VPA rats [ 86 ].…”

“…One study that did so found the habituation rate of the N1 amplitude was lower in Fmr1 −/− mice, but only at presentation rates greater than one stimulus per second [70]. This difference in Chrna7 (18) , Cntnap2 (70) , Drd2 (42) , Mecp2 (35,86) , Wnt1 P1 Many studies with Fmr1 −/− mice have found no difference in the amplitude of the P1 peak, though a recent study using a higher number of channels found an increased P1 in Fmr1 −/− mice compared to WTs [55,60,67,130,147]. The P1 amplitude is generally not different to WTs in other ASD models, with the exception of 15q13.3 deletion mice [48,57,64,121].…”

A bibliometric analysis of autism spectrum disorder signaling pathways research in the past decade

“…Researchers have explored its effects on fetal neural development by injecting propionic acid into pregnant mice to simulate a potential environmental factor, i.e., drug exposure, during pregnancy ( 55 ). Propionic acid is an antiepileptic drug that has been found to be associated with ASD risk.…”