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 Viviana; García Sánchez, José Manuel; Anadón Baselga, María José; Lobo Alonso, Margarita; García Lobo, Jimena; Frejo Moya, María Teresa; Sola Vendrell, Emma; Pelayo Alarcón, Adela; Pino Sans, Javier Del

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

Download

Manganese induced ROS and AChE variants.pdf (3.72 MB)

Official URL

https://www.sciencedirect.com/science/article/pii/S0278691519300626

Publication date

2019

Publisher

Elsevier

Citations

Exportar

URI

https://hdl.handle.net/20.500.14352/100472

Citation

Manganese 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) 583-594

Abstract

Manganese (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.