Air Pollution Exposure Alters Expression of Genes in Human Neurons Previously Implicated in ASD

Background: The link between air pollution and an increased risk of autism spectrum disorder (ASD) is well established. While some forms of ASD originate due to genetic mutations, environmental factors play a large role in epigenetic changes leading to altered brain development. There exists a need for better understanding of molecular changes and biological pathways impacted by model air pollutants.

Objectives: Expose cortical neural progenitor cells to diesel particulate matter (DPM; concentrations 10, 20, 50, 100 ug/mL) to understand the impact on molecular and biological pathways, and the expression of genes associated with ASD. RNA-seq differential gene expression (DE) contrasting each DPM exposure concentration versus control determined biological pathway enrichment using Gene Ontology.

Methods: ReNcell CX neural progenitor cells were exposed to DPM for 24 hours. Following exposure, four biological replicates of each DPM dose were used to extract RNA for RNAseq.

Results: Comparison of DE genes (pval < 0.05) to the Simons Foundation Autism Research Initiative (SFARI) database showed the number of ASD-related genes increased as DPM dose increased. Dose 10 ug/mL and 20 ug/mL had 30 genes, 7 classified as syndromic. Dose 10 ug/mL had two genes associated with Rett Syndrome, CDKL5 and FOXG1, as well as FOXP1. Dose 50 ug/mL had 34 genes and 8 syndromic genes, including DEAF1. Dose 100 ug/mL had 46 genes and 9 syndromic genes including DMD, CHD2 and CDKL5. The majority of these genes were expressed higher in DPM-treated samples than control. In addition, pathway overrepresentation included chromatin remodeling, regulation of telomere maintenance, translation initiation factor activity, DNA replication regulation and endocytosis.

Conclusions: Neural progenitor cell exposure to DPM resulted in a dose dependent increase in differentially expressed genes associated with ASD. The rise in syndromic genes is particularly interesting and warrants further investigation. Furthermore, pathways associated with modifications to DNA were overrepresented due to DPM exposure showing this environmental factor does influence the biological pathways.