Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Laura Lagostena
* ORCID logo ,
Davide Rotondo
ORCID logo ,
Davide Gualandris
ORCID logo ,
Antonio Calisi
ORCID logo ,
Candida Lorusso
ORCID logo ,
Valeria Magnelli
* ORCID logo ,
Francesco Dondero
* ORCID logo
Version 1 : Received: 16 October 2024 / Approved: 18 October 2024 / Online: 21 October 2024 (11:42:42 CEST)

How to cite: Lagostena, L.; Rotondo, D.; Gualandris, D.; Calisi, A.; Lorusso, C.; Magnelli, V.; Dondero, F. 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. Preprints 2024, 2024101469. https://doi.org/10.20944/preprints202410.1469.v1 Lagostena, L.; Rotondo, D.; Gualandris, D.; Calisi, A.; Lorusso, C.; Magnelli, V.; Dondero, F. 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. Preprints 2024, 2024101469. https://doi.org/10.20944/preprints202410.1469.v1

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, revealing a dose-dependent reduction in cell viability 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.

Keywords

electrophysiology; GABAergic signaling; neurotoxicity; PFAS; persistence; toxicology

Subject

Biology and Life Sciences, Toxicology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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