Manganese induced ROS and AChE variants alteration leads to SN56 basal forebrain cholinergic neuronal loss after acute and long-term treatment

Moyano-Cires Ivanoff, Paula VivianaGarcía Sánchez, José ManuelAnadón Baselga, María JoséLobo Alonso, MargaritaGarcía Lobo, JimenaFrejo Moya, María TeresaSola Vendrell, EmmaPelayo Alarcón, AdelaPino Sans, Javier Del2024-02-082024-02-082019Manganese induced ROS and AChE variants alteration leads to SN56 basal forebrain cholinergic neuronal loss after acute and long-term treatment. Paula Moyano, Jose Manuel García, Maria Jose Anadon, Margarita Lobo, Jimena Garcia, Maria Teresa Frejo, Emma Sola, Adela Pelayo, Javier Del Pino. Food and Chemical Toxicology 125 (2019) 583-5940278-691510.1016/j.fct.2019.02.012https://hdl.handle.net/20.500.14352/100472Manganese (Mn) induces cognitive disorders and basal forebrain (BF) cholinergic neuronal loss, involved on learning and memory regulation, which could be the cause of such cognitive disorders. However, the mechanisms through which it induces these effects are unknown. We hypothesized that Mn could induce BF cholinergic neuronal loss through oxidative stress generation, cholinergic transmission and AChE variants alteration that could explain Mn cognitive disorders. This study shows that Mn impaired cholinergic transmission in SN56 cholinergic neurons from BF through alteration of AChE and ChAT activity and CHT expression. Moreover, Mn induces, after acute and long-term exposure, AChE variants alteration and oxidative stress generation that leaded to lipid peroxidation and protein oxidation. Finally, Mn induces cell death on SN56 cholinergic neurons and this effect is independent of cholinergic transmission alteration, but was mediated partially by oxidative stress generation and AChE variants alteration. Our results provide new understanding of the mechanisms contributing to the harmful effects of Mn on cholinergic neurons and their possible involvement in cognitive disorders induced by Mn.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Manganese induced ROS and AChE variants alteration leads to SN56 basal forebrain cholinergic neuronal loss after acute and long-term treatmentjournal articlehttps://doi.org/10.1016/j.fct.2019.02.01230738988https://pubmed.ncbi.nlm.nih.gov/30738988/restricted access61Basal forebrain neuronsManganeseAcetylcholine transferase (ChAT)Acetylcholine esterase (AChE)Cell deathHigh-affinity choline transporter (CHT)Oxidative stressToxicología (Medicina)Neurociencias (Medicina)3214 Toxicología3205.07 Neurología