RT Journal Article
T1 Dysregulation of prostaglandine E2 and BDNF signaling mediated by estrogenic dysfunction induces primary hippocampal neuronal cell death after single and repeated paraquat treatment
A1 Moyano-Cires Ivanoff, Paula Viviana
A1 Sanjuan, Javier
A1 García Sánchez, José Manuel
A1 Anadón Baselga, María José
A1 Naval López, María Victoria
A1 Sola Vendrell, Emma
A1 García Lobo, Jimena
A1 Frejo Moya, María Teresa
A1 Pino Sans, Javier Del
AB Paraquat (PQ) produces hippocampal neuronal cell death and cognitive dysfunctions after unique and continued exposure, but the mechanisms are not understood. Primary hippocampal wildtype or βAPP-Tau silenced cells were co-treated with PQ with or without E2, N-acetylcysteine (NAC), NS-398 (cyclooxygenase-2 inhibitor), MF63 (PGES-1 inhibitor) and/or recombinant brain-derived neurotrophic factor (BDNF) during one- and fourteen-days to studied PQ effect on prostaglandin E2 (PGE2) and BDNF signaling and their involvement in hyperphosphorylated Tau (pTau) and amyloid-beta (Aβ) protein formation, and oxidative stress generation, that lead to neuronal cell loss through estrogenic disruption, as a possible mechanism of cognitive dysfunctions produced by PQ. Our results indicate that PQ overexpressed cyclooxygenase-2 that leads to an increase of PGE2 and alters the expression of EP1-3 receptor subtypes. PQ induced also a decrease of proBDNF and mature BDNF levels and altered P75NTR and tropomyosin receptor kinase B (TrkB) expression. PQ induced PGE2 and BDNF signaling dysfunction, mediated through estrogenic disruption, leading to Aβ and pTau proteins synthesis, oxidative stress generation and finally to cell death. Our research provides relevant information to explain PQ hippocampal neurotoxic effects, indicating a probable explanation of the cognitive dysfunction observed and suggests new therapeutic strategies to protect against PQ toxic effects.
PB Elsevier
SN 0278-6915
YR 2020
FD 2020-10-01
LK https://hdl.handle.net/20.500.14352/116626
UL https://hdl.handle.net/20.500.14352/116626
LA eng
NO Moyano, P., Sanjuan, J., García, J. M., Anadon, M. J., Naval, M. V., Sola, E., ... & Del Pino, J. (2020). Dysregulation of prostaglandine E2 and BDNF signaling mediated by estrogenic dysfunction induces primary hippocampal neuronal cell death after single and repeated paraquat treatment. Food and Chemical Toxicology, 144, 111611.
NO Author contributions: Paula Moyano: Methodology, Investigation, Writing - original draft, Writing - review & editing. Javier Sanjuan: Methodology, Investigation, Writing - original draft, Writing - review & editing. José Manuel García: Methodology, Investigation, Validation, Writing - review & editing. María José Anadon: Data curation, Writing - review & editing. Maria Victoria Naval: Formal analysis, Data curation. Emma Sola: Investigation, Visualization. Jimena García: Investigation, Validation. María Teresa Frejo: Formal analysis, Writing - review & editing. Javier del Pino: Conceptualization, Methodology, Project administration, Supervision, Writing - review & editing.
NO Banco Santander - UCM
DS Docta Complutense
RD 5 abr 2025