Influence of the Aryl Hydrocarbon Receptor Activating Environmental Pollutants on Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is an umbrella term that includes many different disorders that affect the development, communication, and behavior of an individual. Prevalence of ASD has risen exponentially in the past couple of decades. ASD has a complex etiology and traditionally recognized risk factors only account for a small percentage of incidence of the disorder. Recent studies have examined factors beyond the conventional risk factors (e.g., environmental pollution). There has been an increase in air pollution since the beginning of industrialization. Most environmental pollutants cause toxicities through activation of several cellular receptors, such as the aryl hydrocarbon receptor (AhR)/cytochrome P450 (CYPs) pathway. There is little research on the involvement of AhR in contributing to ASD. Although a few reviews have discussed and addressed the link between increased prevalence of ASD and exposure to environmental pollutants, the mechanism governing this effect, specifically the role of AhR in ASD development and the molecular mechanisms involved, have not been discussed or reviewed before. This article reviews the state of knowledge regarding the impact of the AhR/CYP pathway modulation upon exposure to environmental pollutants on ASD risk, incidence, and development. It also explores the molecular mechanisms involved, such as epigenesis and polymorphism. In addition, the review explores possible new AhR-mediated mechanisms of several drugs used for treatment of ASD, such as sulforaphane, resveratrol, haloperidol, and metformin.

Contrasting Negative Effects of Multipollutant Exposure on Femoral and Spinal Bone Mineral Density: Findings from a Population-based Study in US Adults

“…This differential effect may be attributed to the ability of PAHs to disrupt bone homeostasis through interactions between the aryl hydrocarbon receptor (AhR) and the receptor activator of nuclear factor kappa-B ligand (RANKL)-RANK complex [37]. This interaction can disturb bone homeostasis by activating various signaling pathways, including the nuclear factor kappa-B (NF-κB) pathway, the mitogen-activated protein kinase (MAPK) pathway, and the phosphoinositide 3-kinase (PI3K)/Akt pathway [38,39].…”

Maternal Inflammation with Elevated Kynurenine Metabolites Is Related to the Risk of Abnormal Brain Development and Behavioral Changes in Autism Spectrum Disorder

“…AhR is a ligand-activated transcription factor that regulates cell differentiation, proliferation, and cancer imitation. Therefore, activation of AhR is related to the pathogenesis of several diseases, such as cancer, cardiovascular disease, inflammatory diseases, atherosclerosis, and neurodegenerative diseases [ 191 ]. In adults, AhR is widely distributed and expressed in various tissues and regions of the brain [ 192 ].…”

Dynamic and Systemic Perspective in Autism Spectrum Disorders: A Change of Gaze in Research Opens to A New Landscape of Needs and Solutions

“…Placental physiology and placental gene expression are affected by several maternal factors, such as over and under-nutrition, drug and alcohol intake, smoking, a wide range of environmental toxicants, infections and stress [46,47]. Worth noting, a large array of environmental pollutants is activated by the aryl hydrocarbon receptor (AhR)/cytochrome P450 (CYPs) pathway, which in turn affects the epigenetic modulation of ASD-relevant genes [48]. Abruzzo et al (2019) reported a significant increase of the AhR signaling pathway in sera of ASD children [49].…”