Person: Gil De Biedma Elduayen, Leticia
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First Name
Leticia
Last Name
Gil De Biedma Elduayen
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Farmacología y Toxicología
Area
Identifiers
5 results
Search Results
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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: 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 Influx of kynurenine into the brain is involved in the reduction of ethanol consumption induced by Ro 61‐8048 after chronic intermittent ethanol in mice(British Journal of Pharmacology, 2022) Gil De Biedma Elduayen, Leticia; Giménez Gómez, Pablo; Morales Puerto, Nuria; Vidal Casado, Rebeca; Núñez De La Calle, Carlos; Gutiérrez López, María Dolores; O'Shea Gaya, Esther; Colado Megia, María IsabelBackground and Purpose: The kynurenine pathway has been proposed as a target for modulating drug abuse. We previously demonstrated that inhibition of kynurenine 3-monooxygenase (KMO), using Ro 61-8048, reduces ethanol consumption in a binge drinking model. Here, we investigate the effect of the kynurenine pathway modulation in ethanol-dependent mice. Experimental Approach: Adult male and female mice were subjected to a Chronic Intermittent Ethanol (CIE) paradigm. On the last day of CIE, mice were treated with Ro 61-8048, Ro 61-8048 + PNU-120596, a positive allosteric modulator of α7nAChR, and Ro 61-8048 + L-leucine or probenecid, which blocks the influx or efflux of kynurenine from the brain, respectively. Ethanol, water consumption and preference were measured and kynurenine levels in plasma and limbic forebrain were determined. Key Results: Ro 61-8048 decreases consumption and preference for ethanol in both sexes exposed to the CIE model, an effect that was prevented by PNU-120596. The Ro 61-8048-induced decrease in ethanol consumption depends on the influx of kynurenine into the brain. Conclusion and Implications: Inhibition of KMO reduces ethanol consumption and preference in both male and female mice subjected to CIE model by a mechanism involving α7nAChR. Moreover, this centrally-mediated effect depends on the influx of peripheral kynurenine to the brain and can be prolonged by blocking the efflux of kynurenine from the brain. Here, for the first time, we demonstrate that the modulation of the kynurenine pathway is an effective strategy for the treatment of ethanol dependence in both sexes