Person: Leza Cerro, Juan Carlos
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First Name
Juan Carlos
Last Name
Leza Cerro
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Farmacología y Toxicología
Area
Farmacología
Identifiers
26 results
Search Results
Now showing 1 - 10 of 26
- Project number: 273
Item Elaboración de casos clínicos para el aprendizaje basado en casos prácticos: una herramienta pedagógica para la inmersión en la materia de profesores noveles y un recurso didáctico en la metodología de aprendizaje con participación del estudiante(2023) Gutiérrez López, María Dolores; Caballero Collado, Ricardo; Caso, Javier; Delpón Mosquera, María Eva; García Bueno, Borja; Leza Cerro, Juan Carlos; Lizasoain, Ignacio; McDowell Mata, Karina; Morales, Daniel; Moreno Gutiérrez, Laura; Muñoz Madrigal, Jose Luis; O’Shea Gaya, María Esther; Pérez Vizcaíno, Francisco; Tejerina Maria, Teresa; Vidal Casado, Rebeca; Vidal, Alfonso; Martín Hernández, David; Malan-Müller, Stefanie; Olivencia, Miguel Ángel; Morales, Nuria; Núñez de la Calle, Carlos; Vicente Crespo, Maria Elena; Cogolludo Torralba, Ángel LuisEl proyecto propone la elaboración de nuevos casos clínicos que asemejen situaciones reales sobre los que los estudiantes puedan desarrollar un aprendizaje autónomo dirigido por el profesorado en función de los conceptos que sean de interés para cada grupo farmacológico y acercándole a la situación más cercana a su práctica profesional. Los objetivos del proyecto son: 1) Generar una base de nuevos casos clínicos dirigidos a que los estudiantes trabajen sobre grupos de fármacos en un contexto lo más real posible. Los diferentes casos que se elaboren en este proyecto podrán ser utilizados en la docencia de diversas asignaturas impartidas por miembros del departamento de Farmacología y Toxicología. Las sesiones dirigidas al estudio basado en la resolución de casos se plantean como una herramienta docente que tiene como finalidad el desarrollo de competencias transversales como promover la motivación, el trabajo en equipo, la participación de los estudiantes en los debates, así como, fomentar el pensamiento crítico y el conocimiento del método científico. Este tipo de aprendizaje en contexto facilita la integración de los conocimientos y su mayor retención además de la dotar a los estudiantes con las habilidades para fomentar un aprendizaje continuo. 2) Apoyar la formación del profesorado de reciente incorporación, así como del personal investigador que participan como colabores en tareas docentes del departamento y que podrían ser potenciales futuros docentes. Item Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology(Journal of Neuroinflammation, 2021) Ben Afia, Amira; Vila, Èlia; Ormazabal, Aida; Haro, Josep M.; Artuch, Rafael; Ramos, Belén; Mac-Dowell Mata, Karina Soledad; Leza Cerro, Juan Carlos; García Bueno, BorjaBackground: The cortico-cerebellar-thalamic-cortical circuit has been implicated in the emergence of psychotic symptoms in schizophrenia (SZ). The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA). Methods: This work describes alterations in KP in the post-mortem prefrontal cortex (PFC) and cerebellum (CB) of 15 chronic SZ patients and 14 control subjects in PFC and 13 control subjects in CB using immunoblot for protein levels and ELISA for interleukins and QA and KYNA determinations. Monoamine metabolites were analysed by high-performance liquid chromatography and SZ symptomatology was assessed by Positive and Negative Syndrome Scale (PANSS). The association of KP with inflammatory mediators, monoamine metabolism and SZ symptomatology was explored. Results: In the PFC, the presence of the anti-inflammatory cytokine IL-10 together with IDO2 and KATII enzymes decreased in SZ, while TDO and KMO enzyme expression increased. A network interaction analysis showed that in the PFC IL-10 was coupled to the QA branch of the kynurenine pathway (TDO-KMO-QA), whereas IL-10 associated with KMO in CB. KYNA in the CB inversely correlated with negative and general PANSS psychopathology. Although there were no changes in monoamine metabolite content in the PFC in SZ, a network interaction analysis showed associations between dopamine and methoxyhydroxyphenylglycol degradation metabolite. Direct correlations were found between general PANSS psychopathology and the serotonin degradation metabolite, 5-hydroxyindoleacetic acid. Interestingly, KYNA in the CB inversely correlated with 5-hydroxyindoleacetic acid in the PFC. Conclusions: Thus, this work found alterations in KP in two brain areas belonging to the cortico-cerebellar-thalamic-cortical circuit associated with SZ symptomatology, with a possible impact across areas in 5-HT degradation.Item Paliperidone reverts Toll-like receptor 3 signaling pathway activation and cognitive deficits in a maternal immune activation mouse model of schizophrenia(Neuropharmacology, 2017) Mac-Dowell Mata, Karina Soledad; Munarriz Cuezva, Eva; Caso Fernández, Javier Rubén; Muñoz Madrigal, José Luis; Zabala, Arantzazu; Meana, J. Javier; García Bueno, Borja; Leza Cerro, Juan CarlosThe pathophysiology of psychotic disorders is multifactorial, including alterations in the immune system caused by exogenous or endogenous factors. Epidemiological and experimental studies indicate that infections during the gestational period represent a risk factor to develop schizophrenia (SZ) along lifetime. Here, we tested the hypothesis that the antipsychotic paliperidone regulates immune-related brain effects in an experimental model of SZ. A well described prenatal immune activation model of SZ in mice by maternal injection of the viral mimetic poly(I:C) during pregnancy was used. Young-adult offspring animals (60PND) received paliperidone ip (0.05 mg/kg) for 21 consecutive days. One day after last injection, animals were submitted to a cognitive test and brain frontal cortex (FC) samples were obtained for biochemical determinations. The adults showed an activated innate immune receptor TLR-3 signaling pathway, oxidative/nitrosative stress and accumulation of pro-inflammatory mediators such as nuclear transcription factors (i.e., NFκB) and inducible enzymes (i.e., iNOS) in FC. Chronic paliperidone blocked this neuroinflammatory response possibly by the synergic activation and preservation of endogenous antioxidant/anti-inflammatory mechanisms such as NRF2 and PPARγ pathways, respectively. Paliperidone administration also stimulated the alternative polarization of microglia to the M2 anti-inflammatory profile. In addition, paliperidone treatment improved spatial working memory deficits of this SZ-like animal model. In conclusion, chronic administration of paliperidone to young-adult mice prenatally exposed to maternal immune (MIA) challenge elicits a general preventive anti-inflammatory/antioxidant effect at both intracellular and cellular polarization (M1/M2) level in FC, as well as ameliorates specific cognitive deficits.Item Paliperidone Prevents Brain Toll-Like Receptor 4 Pathway Activation and Neuroinflammation in Rat Models of Acute and Chronic Restraint Stress(International Journal of Neuropsychopharmacology, 2015) Mac-Dowell Mata, Karina Soledad; Caso Fernández, Javier Rubén; Martín Hernández, D.; Muñoz Madrigal, José Luis; Leza Cerro, Juan Carlos; García Bueno, BorjaBackground: Alterations in the innate immune/inflammatory system have been proposed to underlie the pathophysiology of psychotic disease, but the mechanisms implicated remain elusive. The main agents of the innate immunity are the family of toll-like receptors (TLRs), which detect circulating pathogen-associated molecular patterns and endogenous damage-associated molecular patterns (DAMPS). Current antipsychotics are able to modulate pro- and anti-inflammatory pathways, but their actions on TLRs remain unexplored. Methods: This study was conducted to elucidate the effects of paliperidone (1mg/Kg i.p.) on acute (6 hours) and chronic (6 hours/day during 21 consecutive days) restraint stress-induced TLR-4 pathway activation and neuroinflammation, and the possible mechanism(s) related (bacterial translocation and/or DAMPs activation). The expression of the elements of a TLR-4-dependent proinflammatory pathway was analyzed at the mRNA and protein levels in prefrontal cortex samples. Results: Paliperidone pre-treatment prevented TLR-4 activation and neuroinflammation in the prefrontal cortices of stressed rats. Regarding the possible mechanisms implicated, paliperidone regulated stress-induced increased intestinal inflammation and plasma lipopolysaccharide levels. In addition, paliperidone also prevented the activation of the endogenous activators of TLR-4 HSP70 and HGMB-1. Conclusions: Our results showed a regulatory role of paliperidone on brain TLR-4, which could explain the therapeutic benefits of its use for the treatment of psychotic diseases beyond its effects on dopamine and serotonin neurotransmission. The study of the mechanisms implicated suggests that gut-increased permeability, inflammation, and bacterial translocation of Gram-negative microflora and HSP70 and HGMB1 expression could be potential adjuvant therapeutic targets for the treatment of psychotic and other stress-related psychiatric pathologies.Item Study of Microbiota in MDD(2020) Caso Fernández, Javier Rubén; Leza Cerro, Juan Carlos; MacDowell Mata, Karina SoledadRaw Data: Sample ID, Relative abundances and Genera ReadsItem The interplay between functioning problems and symptoms in first episode of psychosis: An approach from network analysis(Journal of Psychiatric Research, 2021) Ana Izquierdo; María Cabello; Itziar Leal; Blanca Mellor-Marsá; Miriam Ayora; María-Fe Bravo-Ortiz; Ángela Ibáñez; Karina S. MacDowell; Norberto Malpica; Enrique Baca-García; Natalia E. Fares-Otero; Helena Melero; Pilar López-García; Covadonga M. Díaz-Caneja; Jose Luis Ayuso-Mateos; Manuel Durán-Cutilla; Jessica Merchán-Naranjo; Roberto Mediavilla-Torres; Ainoa Muñoz-Sanjosé; Luis Sanchez-Pastor; Monica Dompablo; Patricia Fernández-Martín; Pablo Puras-Rico; Lucía Albarracin-García; Melero Carrasco, Helena; Rodríguez Jiménez, Roberto; Díaz Marsa, Marina Francisca; Arango López, Celso; García-Albea Martín, Julia Isabel; Leza Cerro, Juan Carlos; Leticia León QuismondoThe relationship between psychotic symptoms and global measures of functioning has been widely studied. No previous study has assessed so far the interplay between specific clinical symptoms and particular areas of functioning in first-episode psychosis (FEP) using network analysis methods. A total of 191 patients with FEP (age 24.45 ± 6.28 years, 64.9% male) participating in an observational and longitudinal study (AGES-CM) comprised the study sample. Functioning problems were assessed with the WHO Disability Assessment Schedule (WHODAS), whereas the Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity. Network analysis were conducted with the aim of analysing the patterns of relationships between the different dimensions of functioning and PANSS symptoms and factors at baseline. According to our results, the most important nodes were “conceptual disorganization”, “emotional withdrawal”, “lack of spontaneity and flow of conversation”, “delusions”, “unusual thought content”, “dealing with strangers” and “poor rapport”. Our findings suggest that these symptoms and functioning dimensions should be prioritized in the clinical assessment and management of patients with FEP. These areas may also become targets of future early intervention strategies, so as to improve quality of life in this population.Item Risperidone administered during adolescence induced metabolic, anatomical and inflammatory/oxidative changes in adult brain: A PET and MRI study in the maternal immune stimulation animal model(European Neuropsychopharmacology, 2019) Casquero-Veiga, Marta; García-García, David; Pérez-Caballero, Laura; Torres-Sánchez, Sonia; Berrocoso, Esther; Desco, Manuel; Soto-Montenegro, María Luisa; Mac-Dowell Mata, Karina Soledad; Fraguas Herráez, David; Leza Cerro, Juan Carlos; Arango López, CelsoInflammation and oxidative stress (IOS) are considered key pathophysiological elements in the development of mental disorders. Recent studies demonstrated that the antipsychotic risperidone elicits an antiinflammatory effect in the brain. We administered risperidone for 2-weeks at adolescence to assess its role in preventing brain-related IOS changes in the maternal immune stimulation (MIS) model at adulthood. We also investigated the development of volumetric and neurotrophic abnormalities in areas related to the HPA-axis. Poly I:C (MIS) or saline (Sal) were injected into pregnant Wistar rats on GD15. Male offspring received risperidone or vehicle daily from PND35-PND49. We studied 4 groups (8-15 animals/group): Sal-vehicle, MIS-vehicle, Sal-risperidone and MIS-risperidone. [18F]FDG-PET and MRI studies were performed at adulthood and analyzed using SPM12 software. IOS and neurotrophic markers were measured using WB and ELISA assays in brain tissue. Risperidone elicited a protective function of schizophrenia-related IOS deficits. In particular, risperidone elicited the following effects: reduced volume in the ventricles and the pituitary gland; reduced glucose metabolism in the cerebellum, periaqueductal gray matter, and parietal cortex; higher FDG uptake in the cingulate cortex, hippocampus, thalamus, and brainstem; reduced NFκB activity and iNOS expression; and increased enzymatic activity of CAT and SOD in some brain areas. Our study suggests that some schizophrenia-related IOS changes can be prevented in the MIS model. It also stresses the need to search for novel strategies based on anti-inflammatory compounds in risk populations at early stages in order to alter the course of the disease.Item Noradrenaline in Alzheimer's Disease: A New Potential Therapeutic Target(2022) Muñoz Madrigal, José Luis; López Gutiérrez, Irene; Dello Russo, Cinzia; Novellino, Fabiana; Caso Fernández, Javier Rubén; García Bueno, Borja; Leza Cerro, Juan CarlosA growing body of evidence demonstrates the important role of the noradrenergic system in the pathogenesis of many neurodegenerative processes, especially Alzheimer’s disease, due to its ability to control glial activation and chemokine production resulting in anti-inflammatory and neuroprotective effects. Noradrenaline involvement in this disease was first proposed after finding deficits of noradrenergic neurons in the locus coeruleus from Alzheimer’s disease patients. Based on this, it has been hypothesized that the early loss of noradrenergic projections and the subsequent reduction of noradrenaline brain levels contribute to cognitive dysfunctions and the progression of neurodegeneration. Several studies have focused on analyzing the role of noradrenaline in the development and progression of Alzheimer’s disease. In this review we summarize some of the most relevant data describing the alterations of the noradrenergic system normally occurring in Alzheimer’s disease as well as experimental studies in which noradrenaline concentration was modified in order to further analyze how these alterations affect the behavior and viability of different nervous cells. The combination of the different studies here presented suggests that the maintenance of adequate noradrenaline levels in the central nervous system constitutes a key factor of the endogenous defense systems that help prevent or delay the development of Alzheimer’s disease. For this reason, the use of noradrenaline modulating drugs is proposed as an interesting alternative therapeutic option for Alzheimer’s disease.Item Gut microbiota, innate immune pathways, and inflammatory control mechanisms in patients with major depressive disorder(Translational Psychiatry, 2021) González-Pinto, Ana; García, Saínza; Diego-Adeliño, Javier de; Carceller-Sindreu, Mar; Sarramea, Fernando; Caballero-Villarraso, Javier; Gracia-García, Patricia; De la Cámara, Concepción; Rodríguez, Juan M.; Caso Fernández, Javier Rubén; Mac-Dowell Mata, Karina Soledad; Leza Cerro, Juan Carlos; Gómez-Lus Centelles, María Luisa; Agüera Ortiz, Luis Fernando; Alba Rubio, ClaudioAlthough alterations in the gut microbiota have been linked to the pathophysiology of major depressive disorder (MDD), including through effects on the immune response, our understanding is deficient about the straight connection patterns among microbiota and MDD in patients. Male and female MDD patients were recruited: 46 patients with a current active MDD (a-MDD) and 22 in remission or with only mild symptoms (r-MDD). Forty-five healthy controls (HC) were also recruited. Psychopathological states were assessed, and fecal and blood samples were collected. Results indicated that the inducible nitric oxide synthase expression was higher in MDD patients compared with HC and the oxidative stress levels were greater in the a-MDD group. Furthermore, the lipopolysaccharide (an indirect marker of bacterial translocation) was higher in a-MDD patients compared with the other groups. Fecal samples did not cluster according to the presence or the absence of MDD. There were bacterial genera whose relative abundance was altered in MDD:Bilophila(2-fold) andAlistipes(1.5-fold) were higher, whileAnaerostipes(1.5-fold) andDialister(15-fold) were lower in MDD patients compared with HC. Patients with a-MDD presented higher relative abundance ofAlistipesandAnaerostipes(1.5-fold) and a complete depletion ofDialistercompared with HC. Patients with r-MDD presented higher abundance ofBilophila(2.5-fold) compared with HC. Thus, the abundance of bacterial genera and some immune pathways, both with potential implications in the pathophysiology of depression, appear to be altered in MDD, with the most noticeable changes occurring in patients with the worse clinical condition, the a-MDD group.Item Microglial CX3CR1 production increases in Alzheimer's disease and is regulated by noradrenaline(Glia, 2021) Muñoz Madrigal, José Luis; González Prieto, Marta; López Gutiérrez, Irene; García Bueno, Borja; Caso Fernández, Javier Rubén; Leza Cerro, Juan Carlos; Ortega Hernández, Adriana; Gómez Garre, DulcenombreThe loss of noradrenergic neurons and subsequent reduction of brain noradrenaline (NA) levels are associated with the progression of Alzheimer's disease (AD). This seems to be due mainly to the ability of NA to reduce the activation of microglial cells. We previously observed that NA induces the production of the chemokine Fractalkine/CX3CL1 in neurons. The activation of microglial CX3CR1, sole receptor for CX3CL1, reduces the activation of microglia, which is known to largely contribute to the neuronal damage characteristic of AD. Therefore, alterations of CX3CR1 production in microglia could translate into the enhancement or inhibition of CX3CL1 anti-inflammatory effects. In order to determine if microglial CX3CR1 production is altered in AD and if NA can control it, CX3CR1 expression and synthesis were analyzed in 5xFAD mice and human AD brain samples. In addition, the effects of NA and its reuptake inhibitor reboxetine were analyzed in microglial cultures and mice respectively. Our results indicate that in AD CX3CR1 production is increased in the brain cortex and that reboxetine administration further increases it and enhances microglial reactivity toward amyloid beta plaques. However, direct administration of NA to primary rat microglia or human HMC3 cells inhibits CX3CR1 production, suggesting that microglia responses to NA may be altered in the absence of CX3CL1-producing neurons or other nonmicroglial external factors.
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