RT Journal Article
T1 Primary hippocampal neuronal cell death induction after acute and repeated paraquat exposures mediated by AChE variants alteration and cholinergic and glutamatergic transmission disruption
A1 Pino Sans, Javier Del
A1 Moyano-Cires Ivanoff, Paula Viviana
A1 Gómez Díaz, Gloria
A1 Anadón Baselga, María José
A1 Díaz Plaza, María Jesús
A1 García Sánchez, José Manuel
A1 Lobo Alonso, Margarita
A1 Pelayo Alarcón, Adela
A1 Sola Vendrell, Emma
A1 Frejo Moya, María Teresa
AB Paraquat (PQ) is a widely used non-selective contact herbicide shown to produce memory and learning deficits after acute and repeated exposure similar to those induced in Alzheimer's disease (AD). However, the complete mechanisms through which it induces these effects are unknown. On the other hand, cholinergic and glutamatergic systems, mainly in the hippocampus, are involved on learning, memory and cell viability regulation. An alteration of hippocampal cholinergic or glutamatergic transmissions or neuronal cell loss may induce these effects. In this regard, it has been suggested that PQ may induce cell death and affect cholinergic and glutamatergic transmission, which alteration could produce neuronal loss. According to these data, we hypothesized that PQ could induce hippocampal neuronal loss through cholinergic and glutamatergic transmissions alteration. To prove this hypothesis, we evaluated in hippocampal primary cell culture, the PQ toxic effects after 24h and 14 consecutive days exposure on neuronal viability and the cholinergic and glutamatergic mechanisms related to it. This study shows that PQ impaired acetylcholine levels and induced AChE inhibition and increased CHT expression only after 14days exposure, which suggests that acetylcholine levels alteration could be mediated by these actions. PQ also disrupted glutamate levels through induction of glutaminase activity. In addition, PQ induced, after 24h and 14days exposure, cell death on hippocampal neurons that was partially mediated by AChE variants alteration and cholinergic and gultamatergic transmissions disruption. Our present results provide new view of the mechanisms contributing to PQ neurotoxicity and may explain cognitive dysfunctions observed after PQ exposure.
PB Elsevier
SN 0300-483X
YR 2017
FD 2017
LK https://hdl.handle.net/20.500.14352/100519
UL https://hdl.handle.net/20.500.14352/100519
LA eng
NO Primary hippocampal neuronal cell death induction after acute and repeated paraquat exposures mediated by AChE variants alteration and cholinergic and glutamatergic transmission disruption. Del Pino J, Moyano P, Diaz GC, Anadon MJ, Diaz MJ, Garcia JM, Lobo M, Pelayo A, Sola E, Frejo MT. Toxicology. 2017 Sep 11;390:88-99
NO Banco Santander
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 6 may 2025