Effects of PM2.5 and gases exposure during prenatal and early-life on autism–like phenotypes in male rat offspring

Abstract

Background: Epidemiological studies have reported associations between elevated air pollution and autism spectrum disorders (ASD). However, we hypothesized that exposure to air pollution that mimics real world scenarios, is a potential contributor to ASD. The exact etiology and molecular mechanisms underlying ASD are not well understood. Thus, we assessed whether changes in OXTR levels may be part of the mechanism linking PM 2.5 /gaseous pollutant exposure and ASD. The current in-vivo study investigated the effect of exposure to fine particulate matter (PM 2.5) and gaseous pollutants on ASD using behavioral and molecular experiments. Four exposure groups of Wistar rats were included in this study: 1) particulate matter and gaseous pollutants exposed (PGE), 2) gaseous pollutants only exposed (GE), 3) autism-like model (ALM) with VPA induction, and 4) clean air exposed (CAE) as the control. Pregnant dams and male pups were exposed to air pollutants from embryonic day (E0) to postnatal day (PND21). Results: The average ± SD concentrations of air pollutants were: PM 2.5 : 43.8 ± 21.1 μg/m 3 , CO: 13.5 ± 2.5 ppm, NO 2 : 0.341 ± 0.100 ppm, SO 2 : 0.275 ± 0.07 ppm, and O 3 : 0.135 ± 0.01 ppm. The OXTR protein level, catalase activity (CAT), and GSH concentrations in the ALM, PGE, and GE rats were lower than those in control group (CAE). However, the decrements in the GE rats were smaller than other groups. Also in behavioral assessments, the ALM, PGE, and GE rats demonstrated a repetitive /restricted behavior and poor social interaction, but the GE rats had weaker responses compared to other groups of rats. The PGE and GE rats showed similar trends in these tests compared to the VPA rats. Conclusions: This study suggested that exposure to ambient air pollution contributed to ASD and that OXTR protein may serve as part of the mechanism linking them.

Early life exposure to air pollution impacts neuronal and glial cell function leading to impaired neurodevelopment

“…[65,87] Male mouse pups gestationally exposed to PM 2.5 had an aberrant expression of oxidative stress biomarkers CAT, OK-1, and SOD, which ultimately led to the downregulation of the oxytocin receptor, known to modulate key neurodevelopmental outcomes and associated with development of autism spectrum disorder. [87,89] It is noteworthy that many of these outcomes are due to air pollution inducing systemic oxidative stress and inflammation in non-neuronal tissues. Although systemic exposure to air pollution has shown to induce oxidative stress in mouse brain, the exacerbating and direct effect of DEP-induced systemic inflammation on neurotoxicity requires further elucidation.…”

“…[65,87,88] Such exposure led to increased intracellular ROS production accompanied by GSH depletion and the activation of NF-κB, [64] lipid peroxidation, signal changes in transport expression and function, a decrease of various tight junction proteins, blood brain barrier compromise and matrix metalloproteinase activation in their offspring. [65,87] Male mouse pups gestationally exposed to PM 2.5 had an aberrant expression of oxidative stress biomarkers CAT, OK-1, and SOD, which ultimately led to the downregulation of the oxytocin receptor, known to modulate key neurodevelopmental outcomes and associated with development of autism spectrum disorder. [87,89] It is noteworthy that many of these outcomes are due to air pollution inducing systemic oxidative stress and inflammation in non-neuronal tissues.…”

Perinatal Exposure to Diesel Exhaust-Origin Secondary Organic Aerosol Induces Autism-Like Behavior in Rats

“…Different hormonal milieu, receptor type and function, and maturation of neural network may contribute the sex-specific effects in ASD. Moreover, compensatory effects of deficient ASD-related genes may protect females from ASD [ 60 ]. Finally, our results indicate that perinatal exposure to DE-SOA may induce autism-like behavior by modulating molecular levels such as neurological and immunological markers in rats.…”

Air pollutants reinforce autism–like behavior in the VPA-Induced – rat model of autism

“…The ethical use of animal models was approved by Shahid Beheshti University of Medical Sciences' Ethics Committee. They were housed in 3 chambers as described previously by Emam et al [93] ( Fig. 7).…”

“…7). It was conducted as previously described by Emam et al [93]. The animal room was located on the roof of the School of Public Health, and Safety of the Shahid Beheshti University of Medical Sciences (35.7991 ̊ N, 51.3947 ̊ E) at a height of 20 m (fourth oor) above the ground .GE-low and GE-high rats in chamber 1 were exposed to ltered ambient air at a ow rate of 20 L/min provided by an oil-free compressor and a HEPA lter (model H13) to remove particulate matter.…”