Galanin (1-15) enhances the behavioral effects of fluoxetine in the forced swimming test: a new therapeutic strategy against depression

The selective serotonergic (5- HT) reuptake inhibitors, including Fluoxetine (FLX), are the most commonly used for treatment of major depression. However, the understanding of the mechanism of action of FLX beyond its effect of elevating 5-HT is limited. The interaction between 5-HT system and neuropeptides signaling could be a key aspect. The neuropeptide Galanin(1-15) [GAL(1-15)], induced a strong depression-like and anxiogenic-like effects in the forced swimming test (FST), the tail suspension test, the open field and the light/dark test. The GALR1-GALR2 heteroreceptor complexes in the dorsal hippocampus and in the dorsal raphe were involved in these effects. We have analyzed the effect of GAL(1–15) on FLX-mediated responses in the FST. We tested the involvement of GALR in the GAL(1–15) effect with the selective GALR2 antagonist M871 and using siRNA GALR2 or GALR1 knockdown rats. Groups of rats received three injections of sc FLX(2.5mg/Kg) or FLX(10mg/Kg) and a single icv injection of a threshold dose of GAL(1-15)(1nmol) 15 minutes before the FST. In a second set of experiments, we determined the involvement of GALR1 and GALR2 in the effect of GAL(1-15) on FLX-mediated action. Groups of rats received three injections of sc FLX(10mg/kg), a single icv injection of GAL(1-15) (1nmol) and the GALR2 antagonist M871 (3nmol) icv alone or in combination. Also, in siRNA GALR1 or GALR2 knockdown rats we coadministered FLX(10mg/Kg) and GAL(1-15)(1nmol). The coadministration of sc FLX(2.5mg/Kg) and icv injection of GAL(1-15)(1nmol) induced antidepressant-like effects with a significant decrease in the immobility (p<0.05). Moreover, an increase in the swimming time (p <0.05) was also observed. The strong enhancement by GAL(1-15) of the antidepressant-like effects mediated by FLX was validated using the effective dose of FLX 10mg/kg. Icv GAL(1-15) significantly decreased the immobility time induced by the effective dose of FLX(10mg/kg) by 50% in the FST (p<0.05). Moreover, an increase of the swimming time by about 40% versus FLX(10mg/kg) group was also observed (p<0.01). The GALR2 antagonist M871 3nmol significantly blocked the GAL(1–15)-induced reduction of the immobility time (p<0.05), and increase in the swimming time (p<0.01) found after coadministration of icv injection of GAL(1-15) and sc FLX(10mg/kg) in the FST. The coadministration of sc FLX(10mg/kg) and icv injection of GAL(1-15) in siRNA GALR1 or GALR2 knockdown animals did not produce a further reduction of the immobility time and a further increase in the swimming time compared to FLX alone. In the current study we describe for the first time that GAL(1-15) enhances the antidepressant-like effects induced by FLX in the FST. Indications were also obtained for the involvement of a GALR1/GALR2 heteroreceptor complex in the GAL (1-15)-mediated actions based on the use of the specific GALR2 antagonist M871 and icv injections of GALR1 siRNA or GALR2 siRNA producing a reduction of GALR1 or GALR2, respectively. The results open up the possibility to use GAL(1-15) as for a combination therapy with FLX as a novel strategy for treatment of depression. This work was supported by grants awarded by Spanish Ministry of Economy (SAF2016-79008-P),Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Immunohistochemical mapping of neurotensin in the alpaca diencephalon

Introduction. The distribution of the immunoreactive cell bodies and fibers containing neurotensin in the alpacadiencephalon was determined by an immunohistochemical technique.Material and methods. The study was carried out in four male alpacas that lived at sea level. Brains of deeplyanesthetized animals were fixed by perfusion with 4% paraformaldehyde. Cryostat sections were stained bya standard immunohistochemical method.Results. Cell bodies containing neurotensin were observed in the zona incerta and hypothalamus. A low/moderatedensity of these cell bodies was observed in the lateral hypothalamic area, anterior and dorsal hypothalamicareas, suprachiasmatic nucleus, periventricular region of the hypothalamus and in the ventromedial hypothalamicnucleus. In both thalamus and hypothalamus, immunoreactive fibers showed a widespread distribution. In thethalamus, a high density of these fibers was mainly found in the midline nuclei, whereas in the hypothalamusa high density was in general observed in the whole structure.Conclusions. In comparison with other mammals, the thalamus of the alpaca showed the most widespread distribution of neurotensin-immunoreactive fibers. The widespread distribution of neurotensin through the alpacadiencephalon suggests that the peptide can be involved in many physiological actions

Adimensionalización de una ecuación diferencial en un problema práctico de ingeniería

This work shows an application of Buckingham Pi theorem to obtain dimensionless parameters from a differential equation used to model an elastic damper system attached to the bumper of a car. Although the original problem was studied by D. A. Peters in his article Optimum Spring-Damper Design for Mass Impact [1], we present to the reader expanded calculations, and computational tools such as C++ and Labview 8.5 are used to obtain optimal values for the spring constant k, and the damping constant c of the system as a function of the impact speed, mass vehicle and expected displacement of the bumper.En este trabajo se muestra la aplicación del teorema Pi de Buckingham para obtener parámetros adimensionales en el proceso de adimensionalizar una ecuación y una consecuencia de esto para el caso particular de un amortiguador elástico conectado al parachoques de un automóvil en la búsqueda de valores óptimos para las constantesde elasticidad del resorte y de atenuación del amortiguador c. Problema estudiado por el ingeniero D. A. Peters en su artículo Optimum Spring-Damper Design for Mass Impact[1]. Por claridad con el lector nos permitimos expandir algunos de los cálculos propuestos en la mencionada publicación y el uso del lenguaje de programación C++ para implementar el método de Newton-Raphson. Finalmente se muestra el instrumentovirtual Labview 8.5 que se construyó para el sistema con el objetivo de obtener los mejores valores de k y c

The graphene oxide species induce a different biological response in SN4741 Parkinson cell line

Introduction: Graphene Oxide (GO)has recently emerged as a reliable material to create scaffolds for the neural tissue because of its biocompatibility, electroconductive and physicochemical properties. Graphene is a 2-dimensional material consisting of rings of carbon atoms with an excellent electrical conductivity originating in the sp2 hybridized carbons network. Nevertheless, there is not a consensus which kind of graphene oxide is most useful of benefit.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Extrasynaptic Neurotransmission in the Modulation of Brain Function. Focus on the Striatal Neuronal–Glial Networks

Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT) and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR) heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT) and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT) and histamine striatal afferents, the cholinergic interneurons, and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal cellular networks

Uma nova disciplinha para o treinamento de formadores e educadores da area da didática das ciências experimentais

La creciente demanda de la sociedad por un estado saludable físico y psíquico obliga a reflexionar sobre programas formativos para desarrollar la competencia en alimentación (Cabello-Garrido, EspañaRamos y Blanco-López, 2016). Desde la Fundación Española del Corazón (FEC), se promueve que para una dieta cardiosaludable el saber qué comprar es clave para un corazón sano (Plaza-Celemín, 2015). Se aboga por una dieta equilibrada donde se apremia los alimentos ricos en hidratos de carbono incluyendo: patatas, legumbres, pan, arroz, pasta, cereales, verduras, hortalizas, frutas y frutos secos a razón de un porcentaje mayor del 50%. Los alimentos ricos en grasas con un porcentaje entre el 3035% eligiendo aceite de oliva virgen y aceite de girasol alto oleico como aceite de fritura. Y entorno al 10-15% de productos ricos en proteínas como lácteos y carnes como publica la prestigiosa revista JAMA (C.B. et al., 2012). Por ello el primer paso para conseguir una dieta equilibrada se inicia por saber qué comprar (Ordovas & Berciano, 2014), aprendiendo a comprar según el contenido nutricional sabiendo analizar el etiquetado los alimentos (García-Ortiz, 2015). La competencia alimentaria no sólo incluye el saber qué comprar en función de su etiquetado analizando las calorías, grasas saturadas, sal y azúcares sino en cómo comerlo y cocinarlo y propiciar el entorno adecuado para alimentarse de manera apropiada (Cabello-Garrido, España-Ramos y Blanco-López, 2016).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

La cardioeducación: una nueva disciplina en la educación infantil

La cardioeducación es una nueva disciplina que hemos creado desde el departamento de Didáctica de las ciencias experimentales y el Departamento de Fisiología Humana para dar formación a los maestros y maestras en formación del grado de Educación Infantil con el fin de mejorar su conocimiento en el tema . La enfermedad cardiovascular es la primera causa de muerte en el mundo y es fundamental generar disciplinas transversales que busquen la mejora en la formación de nuestro alumnado.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Building a Gold Standard Dataset to Identify Articles About Geographic Information Science

To know the overall regional or international scientific production is of vital importance to many areas of knowledge. Nevertheless, in interdisciplinary areas such as Geographic Information Science (GISc) it is not enough to just count papers published in specific journals. Most of them, as is the case of the International Journal of Remote Sensing (IJRS), welcome GISc papers but are not exclusive to that area so the production assignable to authors in the region must consider not only affiliation but also whether or not each paper falls into the theme of GISc. IJRS publishes far more papers than any other GISc journal, so it is important to assess quantitatively how many of them are of GISc. In this work, a representative sample of IJRS articles published over a period of almost 30 years was analyzed using a specific GISc definition. With these data, a manual classification methodology through a set of experts was carried out, and a dataset was built, analyzed, and statistically tested. As a result we estimate that between 47 and 76% of the IJRS articles can be considered from GISc, with a confidence level of 95%. Aside from the primary goal, this set could be used as a gold standard for future classification tasks. It constitutes the first GISc dataset of this kind, that may be used to train artificial intelligence systems capable of performing the same classification automatically and in a massive way. A similar procedure could be applied to other interdisciplinary fields of knowledge as well

Lack of validation of genetic variants associated with anti-tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis

Introduction: In this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations. Methods: The four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients. Results: None of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis. Conclusion: Our data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes

Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept

Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNP