Transcriptomics effects of per- and polyfluorinated alkyl substances in differentiated neuronal cells

Abstract

AbstractPer- and polyfluorinated alkyl substances (PFAS) are ubiquitous in most environments, accumulate in several tissues, and can adversely affect human health. PFAS have been implicated in neurodegenerative and behavioral disorders. However, the mechanisms through which PFAS accumulation in neurons affects biological function remain unknown. In this study, SH-SY5Y neuroblastoma cells were used to investigate how perfluorooctanoic acid (PFOA), perfluorooctansulfonic acid (PFOS), perfluorodecanoic acid (PFDA) perfluorodecanesulfonic acid (PFDS), 8:2 fluorotelomer sulfate (8:2 FTS) and 8:2 fluorotelomer alcohol (8:2 FTOH) exposures influence neuronal health. After a 30 μM-, 24-hour exposure, cells accumulated up to 800 ng PFAS/mg protein. Transcriptomics analysis of control and PFAS-exposed cells revealed 721 genes were differentially expressed across six treatments (padj< 0.05). Eleven of these differentially expressed genes were observed for all treatments, suggesting that these genes are potential markers for neuronal PFAS exposure. In PFOA-treated cells, we observed multiple downregulated genes are enriched for functions related to synaptic growth and neural function. In contrast, upregulated genes in PFOS, PFDS, FTS, and FTOH-treated cells showed enrichment in functions related to response to hypoxia and amino acid metabolism. Overall, our results highlight specific biological processes that potentially underlie negative effects of PFAS on neuronal health.SynopsisPer- and poly fluorinated alkyl substances (PFAS) have been shown to bioaccumulate in human tissues and affect health. This study aims to provide insight into the specific biological processes by which PFAS exposure affects neuronal cells.