Person: O'Shea Gaya, María Esther
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First Name
María Esther
Last Name
O'Shea Gaya
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Farmacología y Toxicología
Area
Farmacología
Identifiers
6 results
Search Results
Now showing 1 - 6 of 6
Item Decreased kynurenine pathway potentiate resilience to social defeat effect on cocaine reward(Neuropharmacology, 2021) Ballestín, Raúl; Ferrer Pérez, Carmen; Reguilón, Marina D; Miñarro López, José; Rodríguez Arias, Marta; Giménez Gómez, Pablo; Gil De Biedma Elduayen, Leticia; Vidal Casado, Rebeca; O'Shea Gaya, María Esther; Colado Megías, María IsabelThe kynurenine (KYN) pathway of tryptophan (TRP) degradation is activated by stress and inflammatory factors. It is now well established that social stress induces the activation of the immune system, with central inflammation and KYN metabolism being two of the main factors linking stress with depression. The aim of the present study was to evaluate the long-lasting changes in the KYN pathway induced by social defeat (SD) associated with the resilience or susceptibility to an increase in the conditioned rewarding effects of cocaine. Mice were exposed to repeated SD and 3 weeks later, a conditioned place preference (CPP) induced by a subthreshold dose of cocaine (1.5 mg/kg) was developed. KYN levels in plasma, cerebellum, hippocampus, striatum and limbic forebrain were studied at the end of the CPP procedure. Changes in the KYN pathway after exposure to pharmacological (oxytocin and indomethacin) and environmental interventions (environmental enrichment) were also evaluated. Our results showed that defeated susceptible (SD-S) mice had higher conditioning scores than resilient mice (SD-R). In addition, although KYN concentration was elevated in all defeated mice, SD-R mice showed smaller increases in KYN concentration in the cerebellum than SD-S mice. Oxytocin or Indomethacin treatment before SD normalized cocaine-induced CPP, although the increase in the KYN pathway was maintained. However, environmental enrichment before SD normalized cocaine-induced CPP and prevented the increase in the KYN pathway. The present study highlights the role of the KYN pathway and anti-inflammatory drugs acting on TRP metabolism as pharmacological targets to potentiate resilience to social stress effects.Item Oxidized soluble guanylyl cyclase causes erectile dysfunction in alcoholic mice(British Journal of Pharmacology, 2023) Olivencia Plaza, Miguel Ángel; Gil De Biedma Elduayen, Leticia; Giménez Gómez, Pablo; Bianca Barreira; Argentina Fernández; Javier Angulo; Colado Megías, María Isabel; O'Shea Gaya, María Esther; Pérez Vizcaíno, FranciscoBackground and purposeAlcohol abuse has been associated with erectile dysfunction (ED), but the implicated molecular mechanisms are unresolved. This study analyses the role of alterations in soluble guanylyl cyclase (sGC) in ED.Experimental approachED was analysed in adult male C57BL/6J mice subjected to the Chronic Intermittent Ethanol (CIE) paradigm. Erectile function was assessed in anaesthetised mice in vivo by evaluating intracavernosal pressure (ICP) and in vitro in isolated mice corpora cavernosa (CC) mounted in a myograph. Protein expression and reactive oxygen species were analysed by western blot and dihydroethidium staining, respectively.Key resultsIn CIE mice, we observed a significant decrease in the relaxant response of the CC to stimulation of NO release from nitrergic nerves by electrical field stimulation, to NO release from endothelial cells by acetylcholine, to the PDE5 inhibitor sildenafil, and to the sGC stimulator riociguat. Conversely, the response to the sGC activator cinaciguat, whose action is independent of the oxidation state of sGC, was significantly enhanced in these CC. The responses to adenylyl cyclase stimulation with forskolin were unchanged. We found an increase in reactive oxygen species in the CC from CIE mice as well as an increase in CYP2E1 and NOX2 protein expression. In vivo pre‐treatment with tempol prevented alcohol‐induced erectile dysfunction.Conclusions and implicationsOur results demonstrate that alcoholic mice show ED in vitro and in vivo due to an alteration in the redox state of sGC and suggest that sGC activators may be effective in ED associated with alcoholism.- Project number: 131
Item Plan de formación docente de jóvenes investigadores pre- y postdoctorales del Departamento de Farmacología y Toxicología.(2019) O'Shea Gaya, María Esther; Pérez Vizcaino, Francisco; Aleixandre De Artiñano, María Amaya; Caballero Collado, Ricardo; Cogolludo Torralba, Ángel Luis; Delpon Mosquera, María Eva; Gutiérrez López, María Dolores; Lizasoain Hernández, Ignacio; Moro Sánchez, María Ángeles; Tejerina Sánchez, María Teresa; Tamargo Menéndez, Juán; Moreno Gutiérrez, Laura; Vicente Crespo, María Elena; Giménez Gómez, Pablo; Ulecia Morón, Cristina; Callejo Arranz, María; Medina Alonso, Violeta; García Utrilla, RaquelLos objetivos que se han alcanzado son los siguientes: 1. Teniendo en cuenta los resultados obtenidos durante el curso 2018-19 (además de los resultados obtenidos en el curso 2017-18) los participantes han alcanzado una formación por encima de lo esperado en Farmacología habiendo asistido a una media de 57% del curso en su primer año de participación (cuando lo estipulado en el Plan de Formacion Docente es del 30%). Además, han superado un 42,3% de la materia entre su primer y segundo año con una calificación media de 8,3. 2. Los jóvenes investigadores han realizado una media de 10 horas de prácticas docentes contabilizando aquellas dedicadas a la asistencia a prácticas como oyentes, el ensayo de las prácticas con tutores y la impartición misma de las sesiones de prácticas. El número de horas está muy limitado por el bajo número de horas prácticas en las asignaturas de Farmacología del Dpto. y el elevado número de jóvenes investigadores incorporados al Dpto. 3. Con todo lo anterior, los jóvenes investigadores han alcanzado la formación en competencias docentes y las horas realizadas han sido acreditadas a las respectivas autoridades de sus becas/contratos. Su participación en la docencia práctica les permitirá en el futuro solicitar un certificado de actividades docentes emitido por las autoridades académicas de la Facultad de Medicina que avalaran su experiencia docente en solicitudes de acreditación a las diferentes figuras de profesor ante la ANECA. Además, el Dpto. de Farmacología y Toxicología ha emitido informes detallados de Aptitud Docente en Farmacología reflejando su participación en el Plan de Formación Docente del Dpto. que podrán ser consideradas en solicitudes a puestos docentes en el futuro. - Project number: 266
Item Gestión de exámenes online. Base de datos de preguntas y desarrollo de software(2021) Pérez Vizcaíno, Francisco; Esquivel Ruiz, Sergio Antonio; Gil De Biedma Elduayen, Leticia; Macías Montero, Miguel; Morales Puerto, Nuria; Núñez De La Calle, Carlos; Olivencia Plaza, Miguel Ángel; Bas Caro, Manuel; Caso Fernandez, Javier Rubén; Cogolludo Torralba, Ángel Luis; García Bueno, Borja; Gutiérrez Lopez, María Dolores; Hurtado Moreno, Olivia; Leza Cerro, Juan Carlos; Moreno Gutiérrez, Laura; O'Shea Gaya, María Esther; Pradillo Justo, Jesús Miguel; Vidal Casado, Rebeca - Project number: 238
Item Base de datos de preguntas y actualización del software. Herramientas para la generación de exámenes presenciales u online(2022) O'Shea Gaya, María Esther; Pérez Vizcaíno, Francisco; Caso Fernández, Javier Rubén; Cogolludo Torralba, Ángel Luis; García Bueno, Borja; Gutiérrez López, María Dolores; Hurtado Moreno, Olivia; Leza Cerro, Juan Carlos; Moreno Gutiérrez, Laura; Pradillo Justo, Jesús Miguel; Vidal Casado, Rebeca; Esquivel Ruiz, Sergio Antonio; Gil De Biedma Elduayen, Leticia; Macías Montero, Miguel; Morales Puerto, Nuria; Núñez De La Calle, Carlos; Olivencia Plaza, Miguel Ángel; Bas Caro, Manuel; Morales Cano, Daniel Item Changes in brain kynurenine levels via gut microbiota and gut‐barrier disruption induced by chronic ethanol exposure in mice(The FASEB Journal, 2019) Giménez Gómez, Pablo; Pérez Hernández, Mercedes; O'Shea Gaya, María Esther; Caso Fernández, Javier Rubén; Martín Hernández, David; Alou Cervera, Luis; Gómez-Lus Centelles, María Luisa; Gutiérrez López, María Dolores; Colado Megías, María IsabelInflammatory processes have been shown to modify tryptophan (Trp) metabolism. Gut microbiota appears to play a significant role in the induction of peripheral and central inflammation. Ethanol (EtOH) exposure alters gut permeability, but its effects on Trp metabolism and the involvement of gut microbiota have not been studied. We analyzed several parameters of gut-barrier and of peripheral and central Trp metabolism following 2 different EtOH consumption patterns in mice, the binge model, drinking in the dark (DID), and the chronic intermittent (CI) consumption paradigm. Antibiotic treatment was used to evaluate gut microbiota involvement in the CI model. Mice exposed to CI EtOH intake, but not DID, show bacterial translocation and increased plasma LPS immediately after EtOH removal. Gut-barrier permeability to FITC-dextran is increased by CI, and, furthermore, intestinal epithelial tight-junction (TJ) disruption is observed (decreased expression of zonula occludens 1 and occludin) associated with increased matrix metalloproteinase (MMP)-9 activity and iNOS expression. CI EtOH, but not DID, increases kynurenine (Kyn) levels in plasma and limbic forebrain. Intestinal bacterial decontamination prevents the LPS increase but not the permeability to FITC-dextran, TJ disruption, or the increase in MMP-9 activity and iNOS expression. Although plasma Kyn levels are not affected by antibiotic treatment, the elevation of Kyn in brain is prevented, pointing to an involvement of microbiota in CI EtOH-induced changes in brain Trp metabolism. Additionally, CI EtOH produces depressive-like symptoms of anhedonia, which are prevented by the antibiotic treatment thus pointing to an association between anhedonia and the increase in brain Kyn and to the involvement of gut microbiota.-Giménez-Gómez, P., Pérez-Hernández, M., O'Shea, E., Caso, J. R., Martín-Hernández, D., Cervera, L. A., Centelles. M. L. G.-L., Gutiérrez-Lopez, M. D., Colado, M. I. Changes in brain kynurenine levels via gut microbiota and gut-barrier disruption induced by chronic ethanol exposure in mice.