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 affects biological function in neurons mostly remain unknown. In this study, SH-SY5Y neuroblastoma cells were used to study the effect of perfluorooctanoic acid (PFOA), perfluorooctansulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorodecanesulfonic acid (PFDS), 8:2 fluorotelomer sulfonate (8:2 FTS) and 8:2 fluorotelomer alcohol (8:2 FTOH) exposures on 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, suggesting PFAS impact different cellular processes in neuronal cells based on their chemical composition and structure. Consistent with this observation, analysis of major lipid classes after exposure to select PFAS showed significant upregulation of fatty acids with PFDA, PFDS and 8:2 FTS and downregulation of triacylglycerols with 8:2 FTOH exposure. Overall, these results suggest that PFAS induce different effectsin vitrodepending on their chemical structures and 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.