RT Journal Article T1 Bisphenol-A Neurotoxic Effects on Basal Forebrain Cholinergic Neurons In Vitro and In Vivo A1 Flores, Andrea A1 Moyano-Cires Ivanoff, Paula Viviana A1 Sola Vendrell, Emma A1 García Sánchez, José Manuel A1 García Lobo, Jimena A1 Frejo Moya, María Teresa A1 Guerra Menéndez, Lucía A1 Labajo González, Elena A1 Lobo Lozano, Inés A1 Abascal, Luisa A1 Pino Sans, Javier Del AB The widely used plasticizer bisphenol-A (BPA) is well-known for producing neurodegeneration and cognitive disorders, following acute and long-term exposure. Although some of the BPA actions involved in these effects have been unraveled, they are still incompletely known. Basal forebrain cholinergic neurons (BFCN) regulate memory and learning processes and their selective loss, as observed in Alzheimer’s disease and other neurodegenerative diseases, leads to cognitive decline. In order to study the BPA neurotoxic effects on BFCN and the mechanisms through which they are induced, 60-day old Wistar rats were used, and a neuroblastoma cholinergic cell line from the basal forebrain (SN56) was used as a basal forebrain cholinergic neuron model. Acute treatment of rats with BPA (40 µg/kg) induced a more pronounced basal forebrain cholinergic neuronal loss. Exposure to BPA, following 1- or 14-days, produced postsynaptic-density-protein-95 (PSD95), synaptophysin, spinophilin, and N-methyl-D-aspartate-receptor-subunit-1 (NMDAR1) synaptic proteins downregulation, an increase in glutamate content through an increase in glutaminase activity, a downregulation in the vesicular-glutamate-transporter-2 (VGLUT2) and in the WNT/β-Catenin pathway, and cell death in SN56 cells. These toxic effects observed in SN56 cells were mediated by overexpression of histone-deacetylase-2 (HDAC2). These results may help to explain the synaptic plasticity, cognitive dysfunction, and neurodegeneration induced by the plasticizer BPA, which could contribute to their prevention. PB MDPI YR 2023 FD 2023-05-28 LK https://hdl.handle.net/20.500.14352/104969 UL https://hdl.handle.net/20.500.14352/104969 LA eng NO Flores A, Moyano P, Sola E, García JM, García J, Frejo MT, et al. Bisphenol-A Neurotoxic Effects on Basal Forebrain Cholinergic Neurons In Vitro and In Vivo. Biology 2023;12:782. https://doi.org/10.3390/biology12060782. NO 2023 Descuento MDPI NO Banco Santander NO Universidad Complutense de Madrid DS Docta Complutense RD 10 abr 2025