Impact of Legacy Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoate (PFOA) on GABA Receptor-Mediated Currents in Neuron-Like Neuroblastoma Cells: Insights into Neurotoxic Mechanisms and Health Implications

Abstract: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are persistent environmental pollutants, raising concerns due to their widespread presence and disruptive biological effects. These compounds are highly stable, allowing them to bioaccumulate in the environment and living organisms, potentially impacting critical physiological functions such as hormonal balance, immune response, and increasing cancer risk. Despite regulatory restrictions, their pervasive nature necessitates further research into their potential effects on cellular and neuronal function. This study first evaluated the cytotoxic effects of PFOS and PFOA on S1 neuroblastoma cells; a dosedependent reduction in cell viability was revealed for PFOS, while PFOA exhibited minimal toxicity until millimolar concentrations. We further investigated their potential to modulate GABAergic neurotransmission using patch-clamp electrophysiology. Both PFOS and PFOA caused a significant but reversible reduction in GABA receptor-mediated currents following one-minute pre-treatment. These findings suggest that PFOS and PFOA can interfere with both cellular viability and GABAergic signaling, providing critical insights into their functional impacts and highlighting the need for further investigation into the long-term consequences of PFAS exposure on nervous system health.