Person: Pino Sans, Javier Del
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First Name
Javier Del
Last Name
Pino Sans
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Veterinaria
Department
FarmacologÃa y ToxicologÃa
Area
ToxicologÃa
Identifiers
12 results
Search Results
Now showing 1 - 10 of 12
Item Primary hippocampal neuronal cell death induction after acute and repeated paraquat exposures mediated by AChE variants alteration and cholinergic and glutamatergic transmission disruption(Toxicology, 2017) Pino Sans, Javier Del; Moyano-Cires Ivanoff, Paula Viviana; Gómez DÃaz, Gloria; Anadón Baselga, MarÃa José; DÃaz Plaza, MarÃa Jesús; GarcÃa Sánchez, José Manuel; Lobo Alonso, Margarita; Pelayo Alarcón, Adela; Sola Vendrell, Emma; Frejo Moya, MarÃa TeresaParaquat (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.Item Efectos del amitraz sobre neurotransmisores monoaminérgicos en el sistema nervioso central de rata(2010) Pino Sans, Javier Del; MartÃnez-Larrañaga, MarÃa Rosa; Anadón Navarro, ArturoPor todo ello, el presente trabajo de investigación tiene dos objetivos: (1) el estudio de las posibles alteraciones en los sistemas serotoninérgico, noradrenérgico y dopaminérgico en regiones del SNC de ratas de edad 30 y 60 dÃas expuestas a dosis múltiples de amitraz, y (2) el estudio de las posibles alteraciones permanentes heredadas en ratas a la edad de 60 dÃas, procedentes de madres a las que se les administró amitraz durante el periodo de la preñez y la lactancia. La elección de la rata como modelo animal experimental se justifica, en general, en que los roedores poseen una serie de ventajas para los estudios toxicológicos, como son su pequeño tamaño, fácil manejo, resistencia a infecciones, corto ciclo de vida y de gestación, y grandes camadas (en número). Además, es un modelo animal aceptado para proporcionar datos que pueden ser incorporados a la evaluación del riesgo para el hombre de pesticidas. En los estudios de niveles de neurotransmisores en el SNC, la rata tiene la ventaja añadida de que por el tamaño de su encéfalo permite una buena localización de las distintas regiones encefálicas. Además, a fecha de hoy existen distintos atlas que detallan la anatomÃa de su sistema nervioso y la distribución de las sustancias neuroactivas (PAROXINOS y WATSON, 1998; TOHYAMA y TAKATSUJI, 1998).Item Cadmium alters heat shock protein pathways in SN56 cholinergic neurons, leading to AB and phosphorylated Tau protein generation and cell death(Food and Chemical Toxicology, 2018) Moyano-Cires Ivanoff, Paula Viviana; GarcÃa Sánchez, José Manuel; Lobo Alonso, Margarita; Anadón Baselga, MarÃa José; Sola Vendrell, Emma; Pelayo Alarcón, Adela; GarcÃa Lobo, Jimena; Frejo Moya, MarÃa Teresa; Pino Sans, Javier DelCadmium, a neurotoxic environmental compound, produces cognitive disorders, although the mechanism remains unknown. Cadmium induces a more pronounced cell death on cholinergic neurons from basal forebrain (BF), mediated, in part, by increase in Aβ and total and phosphorylated Tau protein levels, which may explain cadmium effects on learning and memory processes. Cadmium downregulates the expression of heat shock proteins (HSPs) HSP 90, HSP70 and HSP27, and of HSF1, the master regulator of the HSP pathway. HSPs proteins reduce the production of Aβ and phosphorylated Tau proteins and avoid cell death pathways induction. Thus, we hypothesized that cadmium induced the production of Aβ and Tau proteins by HSP pathway disruption through HSF1 expression alteration, leading to BF cholinergic neurons cell death. Our results show that cadmium downregulates HSF1, leading to HSP90, HSP70 and HSP27 gene expression downregulation in BF SN56 cholinergic neurons. In addition, cadmium induced Aβ and total and phosphorylated Tau proteins generation, mediated partially by HSP90, HSP70 and HSP27 disruption, leading to cell death. These results provide new understanding of the mechanisms contributing to cadmium harmful effects on cholinergic neurons.Item Toxicological and pharmacological evaluation, antioxidant, ADMET and molecular modeling of selected racemic chromenotacrines {11-amino-12-aryl-8,9,10,12-tetrahydro-7H-chromeno[2,3-b]quinolin-3-ols} for the potential prevention and treatment of Alzheimer’s disease(European Journal of Medicinal Chemistry, 2014) Oset Gasque, MarÃa Jesús; González Prieto, MarÃa Pilar; Pérez Peña, Javier; GarcÃa Font, Nuria; Romero MartÃnez, Manuel Alejandro; Pino Sans, Javier Del; Ramos Alonso, Eva; Hadjipavlou-Litina, Dimitra; Soriano, Elena; Chioua, Mourad; Samadi, Abdelouahid; Raghuvanshi, Dushyant S.; Singh, Krishna N.; Marco Contelles, JoséThe pharmacological analysis of racemic chromenotacrines (CT) 1e7, bearing the 11-amino-12-aryl-8,9,10,12-tetrahydro-7H-chromeno[2,3-b]quinolin-3-ol ring skeleton, in a series of experiments targeted to explore their potential use for the treatment of Alzheimer’s disease (AD), is reported. The toxicological evaluation showed that among all these chromenotacrines, CT6 is much less hepatotoxic than tacrine in a range of concentrations from 1 to 300 mM, measured as cell viability in HepG2 cells. Moreover, CT6 did not significantly increase lactate dehydrogenase, aspartate transaminase, and alanine transaminase release in HepG2 cells. Besides,CT6treatment exerts a high protective effect against thelipid peroxidationinduced after H2O2-treated SHSY5Y cells, in a concentration-dependent manner. CT6 showed an excellent antioxidant profile in the AAPH test, and protects against the decrease in cell viability induced by respiratory chain inhibitors (Oligomicyn A/Rotenone)and NO donors in neuronal cultures. This effect could be due to a mixed antiapoptotic and antinecrotic neuroprotective effect at low and intermediate CT6 concentrations, respectively. CT1-7 are potent and selective inhibitors of EeAChE in the submicromolar range. CT3 [IC50 (EeAChE) ¼ 0.007 0.003 mM], and CT6 [IC50 (EeAChE) ¼ 0.041 0.001 mM] are the most potent AChE inhibitors. Kinetic studies on the non-toxic chromenotacrine CT6 showed that this compound behaves as a non-competitive inhibitor (Ki ¼ 0.047 0.003 mM),indicating that CT6 binds at the peripheral anionic site, a fact confirmed by molecular modeling analysis. In silico ADMET analysis showed also that CT6 should have a moderate BBB permeability. Consequently, non-toxic chromenotacrine CT6can be considered as an ttractivemultipotent molecule for the potential treatment of AD.Item Manganese induced ROS and AChE variants alteration leads to SN56 basal forebrain cholinergic neuronal loss after acute and long-term treatment(Food and Chemical Toxicology, 2019) Moyano-Cires Ivanoff, Paula Viviana; GarcÃa Sánchez, José Manuel; Anadón Baselga, MarÃa José; Lobo Alonso, Margarita; GarcÃa Lobo, Jimena; Frejo Moya, MarÃa Teresa; Sola Vendrell, Emma; Pelayo Alarcón, Adela; Pino Sans, Javier DelManganese (Mn) induces cognitive disorders and basal forebrain (BF) cholinergic neuronal loss, involved on learning and memory regulation, which could be the cause of such cognitive disorders. However, the mechanisms through which it induces these effects are unknown. We hypothesized that Mn could induce BF cholinergic neuronal loss through oxidative stress generation, cholinergic transmission and AChE variants alteration that could explain Mn cognitive disorders. This study shows that Mn impaired cholinergic transmission in SN56 cholinergic neurons from BF through alteration of AChE and ChAT activity and CHT expression. Moreover, Mn induces, after acute and long-term exposure, AChE variants alteration and oxidative stress generation that leaded to lipid peroxidation and protein oxidation. Finally, Mn induces cell death on SN56 cholinergic neurons and this effect is independent of cholinergic transmission alteration, but was mediated partially by oxidative stress generation and AChE variants alteration. Our results provide new understanding of the mechanisms contributing to the harmful effects of Mn on cholinergic neurons and their possible involvement in cognitive disorders induced by Mn.Item GuÃa de laboratorio de Toxicogenómica y ToxicologÃa Molecular(2013) Pino Sans, Javier Del; Moyano-Cires Ivanoff, Paula VivianaItem Cadmium induced ROS alters M1 and M3 receptors, leading to SN56 cholinergic neuronal loss, through AChE variants disruption(Toxicology, 2018) Moyano-Cires Ivanoff, Paula Viviana; De Frias, Mariano; Lobo Alonso, Margarita; Anadón Baselga, MarÃa José; Sola Vendrell, Emma; Pelayo Alarcón, Adela; DÃaz Plaza, MarÃa Jesús; Frejo Moya, MarÃa Teresa; Pino Sans, Javier DelCadmium, an environmental neurotoxic compound, produces cognitive disorders, although the mechanism remains unknown. Previously, we described that cadmium induces a more pronounced cell death on cholinergic neurons from basal forebrain (BF). This effect, partially mediated by M1 receptor blockade, triggering it through AChE splices variants alteration, may explain cadmium effects on learning and memory processes. Cadmium has been also reported to induce oxidative stress generation leading to M2 and M4 muscarinic receptors alteration, in hippocampus and frontal cortex, which are necessary to maintain cell viability and cognitive regulation, so their alteration in BF could also mediate this effect. Moreover, it has been reported that antioxidant treatment could reverse cognitive disorders, muscarinic receptor and AChE variants alterations induced by cadmium. Thus, we hypothesized that cadmium induced cell death of BF cholinergic neurons is mediated by oxidative stress generation and this mechanism could produce this effect, in part, through AChE variants altered by muscarinic receptors disruption. To prove this, we evaluated in BF SN56 cholinergic neurons, whether cadmium induces oxidative stress and alters muscarinic receptors, and their involvement in the induction of cell death through alteration of AChE variants. Our results show that cadmium induces oxidative stress, which mediates partially the alteration of AChE variants and M2 to M4 muscarinic receptors expression and blockage of M1 receptor. In addition, cadmium induced oxidative stress generation by M1 and M3 receptors alteration through AChE variants disruption, leading to cell death. These results provide new understanding of the mechanisms contributing to cadmium harmful effects on cholinergic neurons.- Project number: 160
Item Aprendizaje flexible y personalizado para atender la diversidad en el aula, mediante la gamificación, a través del uso integrado de un sistema virtual de respuesta en el aula para dispositivos móviles con acceso a internet y una aplicación de screencasting(2018) Pino Sans, Javier Del; Martin Sopeña, Alejandra; López Salas, Alejandra; De FrÃas González, Mariano; Zeballos Deza, Gabriela; Moyano-Cires Ivanoff, Paula Viviana; GarcÃa Sánchez, José Manuel; Frejo Moya, MarÃa Teresa; Anadón Baselga, MarÃa José; Capó MartÃ, Miguel Andrés; DÃaz Plaza, MarÃa Jesús; Lobo Alonso, Margarita; GarcÃa Lobo, Jimena; Pelayo Alarcon, Adela; Blanco Caneda, Maria Luisa; Peligros Gómez, Isabel; Menarguez Palanca, Javier; López Varela, MarÃa del Carmen; Medina Ortega, Luis; Rodriguez Gil, Yolanda; Agra Pujol, Carolina; Fernández Aceñero, MarÃa Jesús; Sola Vendrell, Emma - Project number: 267
Item 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(2017) Pino Sans, Javier Del; Anadon Baselga, MarÃa Jose; Frejo Moya, MarÃa Teresa; Diaz Plaza, MarÃa Jesús; Capó MartÃ, Miguel Andrés; GarcÃa Lobo, Jimena; Lobo Alonso, Margarita; Moyano-Cires Ivanoff, Paula Viviana; Zeballos Deza, Gabriela; Flores Calle, AndreaIntegración 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. - Project number: 162
Item Evaluación docente dinámica mediante gamificación, con una red social integrada a un sistema de respuesta en el aula a través de una aplicación en cloud para dispositivos móviles con acceso a internet(2015) Pino Sans, Javier DelEl presente proyecto pretende mediante el uso de una aplicación informática de desarrollo propio, que integra una red social y clickers, facilitar la evaluación continua y aumentar la motivación y rendimiento de los estudiantes a un coste muy bajo.