Person:
Pelayo Alarcón, Adela

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First Name
Adela
Last Name
Pelayo Alarcón
URI
https://hdl.handle.net/20.500.14352/79244
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Medicina Legal, Psiquiatría y Patología
Area
Anatomía Patológica
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2019 - 20202
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    Manganese induced ROS and AChE variants alteration leads to SN56 basal forebrain cholinergic neuronal loss after acute and long-term treatment
    (Food and Chemical Toxicology, 2019) 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 (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.
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    Manganese increases Aβ and Tau protein levels through proteasome 20S and heat shock proteins 90 and 70 alteration, leading to SN56 cholinergic cell death following single and repeated treatment
    (Ecotoxicology and Environmental Safety, 2020) Moyano-Cires Ivanoff, Paula Viviana; García Sánchez, José Manuel; García Lobo, Jimena; Anadón Baselga, María José; Naval López, María Victoria; Frejo Moya, María Teresa; Sola Vendrell, Emma; Pelayo Alarcón, Adela; Pino Sans, Javier Del
    Manganese (Mn) produces cholinergic neuronal loss in basal forebrain (BF) region that was related to cognitive dysfunction induced after single and repeated Mn treatment. All processes that generate cholinergic neuronal loss in BF remain to be understood. Mn exposure may produce the reduction of BF cholinergic neurons by increasing amyloid beta (Aβ) and phosphorylated Tau (pTau) protein levels, altering heat shock proteins’ (HSPs) expression, disrupting proteasome P20S activity and generating oxidative stress. These mechanisms, described to be altered by Mn in regions different than BF, could lead to the memory and learning process alteration produced after Mn exposure. The research performed shows that single and repeated Mn treatment of SN56 cholinergic neurons from BF induces P20S inhibition, increases Aβ and pTau protein levels, produces HSP90 and HSP70 proteins expression alteration, and oxidative stress generation, being the last two effects mediated by NRF2 pathway alteration. The increment of Aβ and pTau protein levels was mediated by HSPs and proteasome dysfunction. All these mechanisms mediated the cell decline observed after Mn treatment. Our results are relevant because they may assist to reveal the processes leading to the neurotoxicity and cognitive alterations observed after Mn exposure.