Publication: Efectos neurotóxicos del paraquat sobre el sistema nervioso central de rata y su implicación en el desarrollo de enfermedades neurodegenerativas
Loading...
Files
Official URL
Full text at PDC
Publication Date
2022-10-06
Authors
Advisors (or tutors)
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
Universidad Complutense de Madrid
Citations
Exportar
Abstract
El paraquat (PQ) es un herbicida ampliamente utilizado capaz de causar alteraciones a múltiples niveles orgánicos, destacando sus efectos pulmonares, endocrinos y neurotóxicos. En este sentido, se ha descrito que la intoxicación aguda y crónica con este tóxico ocasiona alteraciones cognitivas, similares a las que se manifiestan en la enfermedad de Alzheimer (EA). Sin embargo, se desconocen los mecanismos completos a través de los cuales el PQ induce estos déficits. A este respecto, se ha descrito que el PQ induce la generación de especies reactivas de oxígeno (ERO), la cual se ha relacionado con la regulación negativa de la expresión de las enzimas antioxidantes de la vía NRF2. Además, se ha descrito que la administración de estrógenos disminuye el nivel de estrés oxidativo celular y que la activación del receptor estrogénico (ER) previene la muerte celular debida a la formación de proteínas ß-amiloideas (Aß) y Tau tras la exposición a PQ. Por lo tanto, el PQ podría mediar estos efectos a través de su actividad antiestrogénica, dando lugar a los déficits de memoria y aprendizaje descritos. Asimismo, se ha descrito que el PQ produce una disminución del número de terminaciones dendríticas en las neuronas del hipocampo, alterando la plasticidad sináptica de las mismas, pudiendo esto derivar en los déficits cognitivos señalados. La correcta formación, tanto en número como en tamaño y funcionalidad, de estas terminaciones se debe a un conjunto de proteínas sinápticas, en cuya regulación se ha observado que interviene el ER, lo cual puede sugerir que la actividad antiestrogénica del PQ sería también capaz de mediar estos efectos sobre las neuronas...
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...
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...
Description
Tesis inédita de la Universidad Complutense de Madrid, Facultad de Veterinaria, Departamento de Farmacología y Toxicología, leída el 09-05-2022