RT Journal Article T1 Single and repeated bisphenol A treatment induces ROS, Aβ and hyperphosphorylated-tau accumulation, and insulin pathways disruption, through HDAC2 and PTP1B overexpression, leading to SN56 cholinergic apoptotic cell death A1 Flores, Andrea A1 Moyano-Cires Ivanoff, Paula Viviana A1 Sola Vendrell, Emma A1 García Sánchez, José Manuel A1 García Lobo, Jimena A1 Anadón Baselga, María José A1 Frejo Moya, María Teresa A1 Naval López, María Victoria A1 Fernández Fernández, María De La Cabeza A1 Pino Sans, Javier Del AB Bisphenol-A (BPA), a polymer component extensively used, produces memory and learning alterations after acute and long-term exposure. However, the mechanisms are not well known. Cortex and hippocampus neuronal networks control cognitive functions, which are innervated by basal forebrain cholinergic neurons (BFCN), and their neurodegeneration induces cognitive dysfunctions. Wild type or protein tyrosine phosphatase 1B (PTP1B), histone deacetylase 2 (HDAC2), tau or β amyloid precursor protein (βAPP) silenced SN56 cells treated with BPA (0.001 μM–100 μM) with or without N-acetylcysteine (NAC; 1 mM), following 1 and 14 days, were used, as a model of BFCN to determine the insulin pathway dysfunction, oxidative stress (OS) generation and amyloid-β (Aβ) and tau proteins accumulation involvement in the BCFN cell death induction, as a possible mechanism that could produce the cognitive disorders reported. BPA-induced BFCN cell death, after 24 h and 14 days of treatment, through insulin pathway dysfunction, OS generation, mediated by NRF2 pathway downregulation, and Aβ and tau proteins accumulation, which were in turn induced by HDAC2 and PTP1B overexpression. This is relevant information to explain the BFCN neurodegeneration mechanisms that could trigger the neurodegeneration in the rest of the regions innerved by them, leading to cognitive disorders. PB Elsevier SN 0278-6915 YR 2022 FD 2022-10-29 LK https://hdl.handle.net/20.500.14352/117076 UL https://hdl.handle.net/20.500.14352/117076 LA eng NO Flores, A., Moyano, P., Sola, E., García, J. M., García, J., Anadon, M. J., ... & Del Pino, J. (2022). Single and repeated bisphenol A treatment induces ROS, Aβ and hyperphosphorylated-tau accumulation, and insulin pathways disruption, through HDAC2 and PTP1B overexpression, leading to SN56 cholinergic apoptotic cell death. Food and Chemical Toxicology, 170, 113500. NO Banco Santander NO Universidad Complutense de Madrid DS Docta Complutense RD 11 abr 2025