Title : SN56 neuronal cell death after 24h and 14days chlorpyrifos exposure through glutamate transmission dysfunction, increase of GSK-3beta enzyme, beta-amyloid and tau protein levels - Moyano_2018_Toxicology_402-403_17 |
Author(s) : Moyano P , Frejo MT , Anadon MJ , Garcia JM , Diaz MJ , Lobo M , Sola E , Garcia J , Del Pino J |
Ref : Toxicology , 402-403 :17 , 2018 |
Abstract :
Chlorpyrifos (CPF) is an organophosphate insecticide described to induce cognitive disorders, both after acute and repeated administration. However, the mechanisms through which it induces these effects are unknown. CPF has been reported to produce basal forebrain cholinergic neuronal cell death, involved on learning and memory regulation, which could be the cause of such cognitive disorders. Neuronal cell death was partially mediated by oxidative stress generation, P75(NTR) and alpha7-nAChRs gene expression alteration triggered through acetylcholinesterase (AChE) variants disruption, suggesting other mechanisms are involved. In this regard, CPF induces Abeta and tau proteins production and activation of GSK3beta enzyme and alters glutamatergic transmission, which have been related with basal forebrain cholinergic neuronal cell death and development of cognitive disorders. According to these data, we hypothesized that CPF induces basal forebrain cholinergic neuronal cell death through induction of Abeta and tau proteins production, activation of GSK-3beta enzyme and disruption of glutamatergic transmission. We evaluated this hypothesis in septal SN56 basal forebrain cholinergic neurons, after 24h and 14days CPF exposure. This study shows that CPF increases glutamate levels, upregulates GSK-3beta gene expression, and increases the production of Abeta and phosphorylated tau proteins and all these effects reduced cell viability. CPF increases glutaminase activity and upregulates the VGLUT1 gene expression, which could mediate the disruption of glutamatergic transmission. Our present results provide new understanding of the mechanisms contributing to the harmful effects of CPF, and its possible relevance in the pathogenesis of neurodegenerative diseases. |
PubMedSearch : Moyano_2018_Toxicology_402-403_17 |
PubMedID: 29665406 |
Moyano P, Frejo MT, Anadon MJ, Garcia JM, Diaz MJ, Lobo M, Sola E, Garcia J, Del Pino J (2018)
SN56 neuronal cell death after 24h and 14days chlorpyrifos exposure through glutamate transmission dysfunction, increase of GSK-3beta enzyme, beta-amyloid and tau protein levels
Toxicology
402-403 :17
Moyano P, Frejo MT, Anadon MJ, Garcia JM, Diaz MJ, Lobo M, Sola E, Garcia J, Del Pino J (2018)
Toxicology
402-403 :17