Gene-environment interactions with air pollutants may play critical role in increasing ASD prevalence.
Study:Air pollution: an emerging risk factor for autism spectrum disorder. Image Credit: Borri_Studio/Shutterstock.com
In a recent review published in Brain Medicine, a group of authors examined air pollution as a key environmental risk factor for autism (a neurodevelopmental disorder affecting social skills and behavior), highlighting gene-environment interactions and neurodevelopmental impacts.
Background
Air pollution has become a prominent environmental health concern, with recent studies linking exposure to pollutants like particulate matter (PM), sulfur dioxide (SO₂), nitrogen oxide (NO), nitrogen dioxide (NO₂), and ozone (O₃) to an increased risk of autism spectrum disorder (ASD).
These pollutants are believed to contribute to ASD through mechanisms including neuroinflammation, oxidative stress, and disruptions in neurotransmitter systems.
Vulnerable populations, particularly pregnant women and young children may face heightened risks due to critical brain development stages. Given the global increase in pollution and rising ASD prevalence, further research is essential to clarify these links and inform preventive strategies.
PM and its neurodevelopmental effects
PM is a well-known category of air pollutant that consists of fine airborne particles PM2.5, which refers to particles less than 2.5 micrometers in diameter, and PM10, which are slightly larger particles, have been studied extensively due to their ability to penetrate deep into the respiratory system. These particles can enter the bloodstream, cross the placental barrier, and reach the fetal brain.
Studies have shown that prenatal exposure to PM10 can adversely impact fetal development, and PM2.5, which penetrates even more deeply, has been associated with an increased risk of ASD when exposure occurs during early pregnancy or preconception periods. Due to these findings, PM is considered a high-priority pollutant for understanding ASD risk.
NO and NO₂
NO and NO₂ are harmful air pollutants primarily released from vehicle emissions and the combustion of industrial fuels. Exposure to these pollutants, particularly during pregnancy and early childhood, can interfere with the normal developmental processes of the brain, such as neuronal migration and myelination.
Recent groundbreaking research has directly linked NO exposure to ASD, making it one of the first pollutants with a clearly defined pathway to ASD risk. The timing of exposure is crucial, as disruptions in brain development during early prenatal and postnatal periods can lead to long-term neurodevelopmental issues.
O₃: A reactive pollutant
O₃ is a highly reactive oxygen molecule formed through chemical reactions between volatile organic compounds and nitrogen oxides. Research by McGuinn et al. has established a connection between O₃ exposure, especially in combination with PM2.5, and an increased risk of ASD.
When exposed during critical developmental windows, such as pregnancy and the first two years of life, ozone may contribute to neurodevelopmental disorders due to its oxidative properties, which can damage brain cells and hinder their development. This association highlights the need for policies to reduce ground-level ozone, especially in urban and industrialized areas.
SO₂ and volatile organic compounds
SO₂ is another toxic pollutant originating from fossil fuel combustion, vehicle emissions, and industrial processes. Studies indicate that maternal exposure to SO₂, particularly during pregnancy and early childhood, is associated with a higher risk of ASD.
Additionally, volatile organic compounds such as benzene, which is commonly found in industrial processes, tobacco smoke, and emissions are of concern. Exposure to these compounds during pregnancy, particularly in combination with other pollutants like NO₂, can have synergistic effects that further increase ASD risk.
Research into SO₂ and volatile compounds suggests that air pollution’s cumulative and mixed effects on neurodevelopment are complex and potent.
Mechanisms linking pollutants to ASD: Neuroinflammation and oxidative Stress
The harmful effects of air pollution on the brain can be traced to several biological mechanisms, including neuroinflammation and oxidative stress. During pregnancy, inhaled pollutants like PM can lead to an inflammatory response in the fetus and trigger neuroinflammation in the developing brain.
An immature blood-brain barrier allows PM to reach fetal brain cells, initiating inflammation within cells like astrocytes and microglia. Pollutants such as NO₂ and PM2.5 can activate toll-like receptors (TLRs) and pathways like Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), which regulate genes associated with inflammation.
Chronic inflammation in the developing brain can lead to disrupted neural networks, a hallmark in many individuals with ASD.
Epigenetic modifications and neurotransmitter imbalances
Air pollution can also cause epigenetic changes, which modify how genes are expressed without altering the Deoxyribonucleic acid (DNA) sequence itself. DNA methylation and histone modification are two such changes that have been observed in relation to air pollution exposure.
These alterations can impact genes that control brain development and immune function, potentially increasing the likelihood of ASD. Additionally, exposure to air pollution disrupts the balance of neurotransmitters like glutamate and Gamma-Aminobutyric Acid (GABA), both essential for normal brain function.
Imbalances in these neurotransmitters, often observed in individuals with ASD, can be induced by pollution exposure and may contribute to the disorder’s characteristic symptoms.
Endocrine disruption and metabolic pathway dysregulation
Certain pollutants, particularly fine PM, act as endocrine disruptors, altering hormone levels that are critical for brain development. This disruption of hormones, such as estrogen and thyroid hormones, during crucial developmental stages, can lead to neurodevelopmental abnormalities, including ASD.
Additionally, exposure to air pollution can dysregulate metabolic pathways involving fatty acids, amino acids, and neurotransmitters, all of which play important roles in neurodevelopment.
Understanding these metabolic effects offers insights into the link between pollution and ASD risk, particularly during the vulnerable perinatal period.
Conclusions
To summarize, the study concludes that air pollution is a significant environmental risk factor for ASD, affecting neurodevelopment through multiple mechanisms, including epigenetic modifications, neuroinflammation, oxidative stress, and endocrine disruption.
Exposure to pollutants such as PM, NO₂, NO, SO2, and O3 during critical developmental windows, particularly in pregnancy and early childhood, increases ASD risk.
