Efectos neurotóxicos del clorpirifos sobre el sistema colinérgico e implicaciones legales del uso del perfil toxicogenómico como biomarcador de toxicidad

Clorpirifós (CPF) es uno de los insecticidas organofosforados (OP) más utilizados en aplicaciones agrícolas y residenciales (Figura 1). El CPF es capaz de causar alteraciones de desarrollo, inmunológicas, y efectos neurotóxicos. Por otra parte, la exposición ocupacional a los OP se ha relacionado, en estudios epidemiológicos en humanos, con déficits neurológicos y neuroconductuales, incluyendo alteraciones de la cognición. En este sentido, el CPF se ha demostrado que produce en ratas tras la administración aguda y repetida, déficits de aprendizaje similares a los inducidos en la enfermedad de Alzheimer (AD). Sin embargo, los mecanismos completos a través del cual el CPF induce estas alteraciones cognitivas son desconocidos..

Guía de laboratorio de Toxicogenómica y Toxicología Molecular

Sección Deptal. de Farmacología y Toxicología (Veterinaria)Fac. de Veterinariapu

Guía de Prácticas de Laboratorio y seminarios de Toxicología Veterinaria

Sección Deptal. de Farmacología y Toxicología (Veterinaria)Fac. de Veterinariapu

Guía de prácticas y seminarios de Fundamentos de Toxicología

Sección Deptal. de Farmacología y Toxicología (Veterinaria)Fac. de Veterinariapu

Guía de Prácticas de Laboratorio y seminarios de Toxicología de los Alimentos

Sección Deptal. de Farmacología y Toxicología (Veterinaria)Fac. de Veterinariapu

Neuroprotective mechanisms of multitarget 7-aminophenanthridin-6(5H)-one derivatives against metal-induced amyloid proteins generation and aggregation

Brain’s metals accumulation is associated with toxic proteins, like amyloid-proteins (Aβ), formation, accumulation, and aggregation, leading to neurodegeneration. Metals downregulate the correct folding, disaggregation, or degradation mechanisms of toxic proteins, as heat shock proteins (HSPs) and proteasome. The 7-amino-phenanthridin-6(5H)-one derivatives (APH) showed neuroprotective effects against metal-induced cell death through their antioxidant effect, independently of their chelating activity. However, additional neuroprotective mechanisms seem to be involved. We tested the most promising APH compounds (APH1-5, 10–100 μM) chemical ability to prevent metal-induced Aβ proteins aggregation; the APH1-5 effect on HSP70 and proteasome 20S (P20S) expression, the metals effect on Aβ formation and the involvement of HSP70 and P20S in the process, and the APH1-5 neuroprotective effects against Aβ proteins (1 μM) and metals in SN56 cells. Our results show that APH1-5 compounds chemically avoid metal-induced Aβ proteins aggregation and induce HSP70 and P20S expression. Additionally, iron and cadmium induced Aβ proteins formation through downregulation of HSP70 and P20S. Finally, APH1-5 compounds protected against Aβ proteins-induced neuronal cell death, reversing partially or completely this effect. These data may help to provide a new therapeutic approach against the neurotoxic effect induced by metals and other environmental pollutants, especially when mediated by toxic proteins

Aprendizaje colaborativo/competitivo mediante gamificación, a través del uso integrado de un mando wiimote como pizarra digital interactiva, un sistema virtual de respuesta en el aula, y dispositivos móviles con acceso a internet

Integración de pizarra digital, una aplicación informática propia como sistema de respuesta (clicker) y otras aplicaciones no propias para facilitar la evaluación continua, aumentar la motivación y rendimiento de los estudiantes a un coste muy bajo

Insulin Signaling Disruption and INF-γ Upregulation Induce Aβ1–42 and Hyperphosphorylated-Tau Proteins Synthesis and Cell Death after Paraquat Treatment of Primary Hippocampal Cells

Acute and long-term paraquat (PQ) exposure produces hippocampal neurodegeneration and cognition decline. Although some mechanisms involved in these effects were found, the rest are unknown. PQ treatment, for 1 and 14 days, upregulated interferon-gamma signaling, which reduced insulin levels and downregulated the insulin pathway through phosphorylated-c-Jun N-terminal-kinase upregulation, increasing glucose levels and the production of Aβ1–42 and phosphorylated-tau, by beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) overexpression and phosphorylated-GSK3β (p-GSK3β; ser9) level reduction, respectively, which induced primary hippocampal neuronal loss. This novel information on the PQ mechanisms leading to hippocampal neurodegeneration could help reveal the PQ actions that lead to cognition dysfunction

Cadmium-induced neurotoxic effects on rat basal forebrain cholinergic system through thyroid hormones disruption

Cadmium (Cd) single and repeated exposure produces cognitive dysfunctions. Basal forebrain cholinergic neurons (BFCN) regulate cognitive functions. BFCN loss or cholinergic neurotransmission dysfunction leads to cognitive disabilities. Thyroid hormones (THs) maintain BFCN viability and functions, and Cd disrupts their levels. However, Cd-induced BFCN damages and THs disruption involvement was not studied. To research this we treated male Wistar rats intraperitoneally with Cd once (1 mg/kg) or repetitively for 28 days (0.1 mg/kg) with/without triiodothyronine (T3, 40 µg/kg/day). Cd increased thyroid-stimulating-hormone (TSH) and decreased T3 and tetraiodothyronine (T4). Cd altered cholinergic transmission and induced a more pronounced neurodegeneration on BFCN, mediated partially by THs reduction. Additionally, Cd antagonized muscarinic 1 receptor (M1R), overexpressed acetylcholinesterase S variant (AChE-S), downregulated AChE-R, M2R, M3R and M4R, and reduced AChE and choline acetyltransferase activities through THs disruption. These results may assist to discover cadmium mechanisms that induce cognitive disabilities, revealing a new possible therapeutic tool

Aprendizaje flexible y personalizado para atender la diversidad en el aula, mediante el uso del flipped learning (aprendizaje invertido), a través del uso integrado de un sistema virtual de respuesta en el aula, y otras herramientas TACs

Integración de una aplicación informática propia como sistema de respuesta (clicker) y diferentes herramientas TCs para facilitar la evaluación continua de forma personalizada, aumentar la motivación y rendimiento de los estudiantes a bajo coste