RT Journal Article
T1 Thyroid Hormone Neuroprotection Against Perfluorooctane Sulfonic Acid Cholinergic and Glutamatergic Disruption and Neurodegeneration Induction
A1 Moyano-Cires Ivanoff, Paula Viviana
A1 Guzmán, Gabriela
A1 Flores, Andrea
A1 García Lobo, Jimena
A1 Guerra Menéndez, Lucía
A1 Sanjuan, Javier
A1 Plaza Hernández, José Carlos
A1 Abascal, Luisa
A1 Mateo Sierra, Olga
A1 Pino Sans, Javier Del
AB Background: Perfluorooctane sulfonic acid (PFOS), a widely used industrial chemical, was reported to induce memory and learning process dysfunction. Some studies tried to reveal the mechanisms that mediate these effects, but how they are produced is still unknown. Basal forebrain cholinergic neurons (BFCN) maintain cognitive function and their selective neurodegeneration induces cognitive decline, as observed in Alzheimer’s disease. PFOS was reported to disrupt cholinergic and glutamatergic transmissions and thyroid hormone action, which regulate cognitive processes and maintain BFCN viability. Objective/Methods: To evaluate PFOS neurodegenerative effects on BFCN and the mechanisms that mediate them, SN56 cells (a neuroblastoma cholinergic cell line from the basal forebrain) were treated with PFOS (0.1 µM to 40 µM) with or without thyroxine (T3; 15 nM), MK-801 (20 µM) or acetylcholine (ACh; 10 µM). Results: In the present study, we found that PFOS treatment (1 or 14 days) decreased thyroid receptor α (TRα) activity by decreasing its protein levels and increased T3 metabolism through increased deiodinase 3 (D3) levels. Further, we observed that PFOS treatment disrupted cholinergic transmission by decreasing ACh content through decreased choline acetyltransferase (ChAT) activity and protein levels and through decreasing muscarinic receptor 1 (M1R) binding and protein levels. PFOS also disrupted glutamatergic transmission by decreasing glutamate content through increased glutaminase activity and protein levels and through decreasing N-methyl-D-aspartate receptor subunit 1 (NMDAR1); effects mediated through M1R disruption. All these effects were mediated through decreased T3 activity and T3 supplementation partially restored to the normal state. Conclusions: These findings may assist in understanding how PFOS induces neurodegeneration, and the mechanisms involved, especially in BFCN, to explain the process that could lead to cognitive dysfunction and provide new therapeutic tools to treat and prevent its neurotoxic effects.
PB MDPI
YR 2024
FD 2024
LK https://hdl.handle.net/20.500.14352/114092
UL https://hdl.handle.net/20.500.14352/114092
LA eng
NO Moyano, P.; Guzmán, G.; Flores, A.; García, J.; GuerraMenéndez, L.; Sanjuan, J.; Plaza, J.C.; Abascal, L.; Mateo, O.; Del Pino, J. Thyroid Hormone Neuroprotection Against Perfluorooctane Sulfonic Acid Cholinergic and Glutamatergic Disruption and Neurodegeneration Induction. Biomedicines 2024, 12, 2441. https://doi.org/10.3390/ biomedicines12112441
NO Conceptualization, J.D.P., P.M., A.F. and G.G.; methodology, J.D.P., P.M. and A.F.; software, J.D.P., P.M. and A.F.; validation, J.D.P., P.M., A.F. and O.M.; formal analysis, O.M.; Biomedicines 2024, 12, 2441 19 of 23 investigation, J.D.P., P.M., A.F., L.G.-M., J.C.P., O.M., L.A., J.G., J.S. and G.G.; data curation, J.D.P., P.M. and A.F.; writing—original draft preparation, J.D.P., P.M. and G.G.; visualization, L.G.-M.; supervision, J.D.P., P.M. and A.F.; project administration, J.D.P.; funding acquisition, J.D.P. All authors have read and agreed to the published version of the manuscript.
NO Banco Santander - Universida Complutense de Madrid
NO Fundación Alborada
DS Docta Complutense
RD 17 abr 2025