Moyano-Cires Ivanoff, Paula VivianaFlores Calle, AndreaSan Juan, JavierGarcía Lobo, JimenaAnadón Baselga, María JoséPlaza Hernández, José CarlosNaval López, María VictoriaFernández Fernández, María De La CabezaGuerra Menéndez, LucíaPino Sans, Javier Del2024-09-302024-09-302024Moyano, P., Flores, A., San Juan, J., García, J., Anadón, M. J., Plaza, J. C., Naval, M. V., Fernández, M. C., Guerra-Menéndez, L., & Del Pino, J. (2024). Imidacloprid unique and repeated treatment produces cholinergic transmission disruption and apoptotic cell death in SN56 cells. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 193, 114988. Advance online publication. https://doi.org/10.1016/j.fct.2024.1149880278-691510.1016/j.fct.2024.114988https://hdl.handle.net/20.500.14352/108456Este trabajo ha sido financiado por la beca de investigación 172C126PMA de Alborada Foundation/Cátedra Extraordinaria de Patología y Medioambiente, UCMImidacloprid (IMI), the most widely used worldwide neonicotinoid biocide, produces cognitive disorders after repeated and single treatment. However, little was studied about the possible mechanisms that produce this effect. Cholinergic neurotransmission regulates cognitive function. Most cholinergic neuronal bodies are present in the basal forebrain (BF), regulating memory and learning process, and their dysfunction or loss produces cognition decline. BF SN56 cholinergic wild-type or acetylcholinesterase (AChE), β-amyloid-precursor-protein (βAPP), Tau, glycogen-synthase-kinase-3-beta (GSK3β), beta-site-amyloid-precursor-protein-cleaving enzyme 1 (BACE1), and/or nuclear-factor-erythroid-2-related-factor-2 (NRF2) silenced cells were treated for 1 and 14 days with IMI (1 μM-800 μM) with or without recombinant heat-shock-protein-70 (rHSP70), recombinant proteasome 20S (rP20S) and with or without N-acetyl-cysteine (NAC) to determine the possible mechanisms that mediate this effect. IMI treatment for 1 and 14 days altered cholinergic transmission through AChE inhibition, and triggered cell death partially through oxidative stress generation, AChE-S overexpression, HSP70 downregulation, P20S inhibition, and Aβ and Tau peptides accumulation. IMI produced oxidative stress through reactive oxygen species production and antioxidant NRF2 pathway downregulation, and induced Aβ and Tau accumulation through BACE1, GSK3β, HSP70, and P20S dysfunction. These results may assist in determining the mechanisms that produce cognitive dysfunction observed following IMI exposure and provide new therapeutic tools.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article1873-6351https://doi.org/10.1016/j.fct.2024.11498839251036https://www.sciencedirect.com/science/article/pii/S0278691524005544?via%3Dihub#ack0010open access615.9ImidaclopridSN56 basal forebrain cholinergic neuronsAChEHSP70Proteasome 20SAβTauToxicología (Farmacia)3214 Toxicología