Efectos neurotóxicos del paraquat sobre el sistema nervioso central de rata y su implicación en el desarrollo de enfermedades neurodegenerativas

Abstract

Paraquat (PQ) is a widely used herbicide that causes alterations at multiple organic levels, including pulmonary, endocrine and neurotoxic effects. In this regard, PQ has been reported to produce cognitive disorders after acute and repeated exposure similar to those observed in Alzheimer´s disease (AD). However, the complete mechanisms through which PQ induces these deficits are unknown.In relation with this, PQ was reported to induce reactive oxygen species (ROS) generation, which have been related to NRF2 pathway enzymes downregulation. In addition, estradiol (E2) administration has been reported to decrease cellular oxidative stress levels, and estrogen receptor (ER) activation has been reported to avoid cell death caused by ß-amyloid (Aß) and Tau proteins production after PQ exposure. Therefore, PQ could mediate these effects through its antiestrogenic action, leading to the memory and learning disorders described. Likewise, PQ was described to produce dendritic spine number decline in hippocampal neurons, disrupting synaptic plasticity, which this could lead to the cognitive disorders indicated. The correct development of these spines, both in number, size and functionality, is due to several synaptic proteins, which are regulated by ER, so this may suggest that PQ antiestrogenic activity would also be able to mediate these effects in neurons...