RELACIÓN ENTRE LA MICROBIOTA Y LA PÉRDIDA DE PESO

En la sociedad actual, la obesidad y el sobrepeso constituyen un grave problema de salud pública, tanto por su elevada prevalencia como por las enfermedades que suelen acompañarlas.En los últimos años, varios estudios han demostrado una relación entre la microbiota intestinal y su influencia sobre la pérdida de peso. Si bien es cierto que con la evidencia actual no está claro el perfil de microbiota al que se le atribuye el desarrollo de obesidad, en modelos animales parece verse relacionado con la mayor prevalencia de bacterias del filo Firmicutes, en detrimento de bacterias del filo Bacteroidetes. Otros factores implicados podrían ser la disminución de la diversidad de la microbiota intestinal o posibles cambios funcionales en esta. Por todo ello, son necesarios más estudios en el campo de la microbiota en humanos para esclarecer conclusiones.Por otra parte, los probióticos si han sido estudiados en humanos en numerosos estudios. Se ha visto que presentan un potencial efecto beneficioso. A pesar de ello, es preciso concretar qué cepas deben recomendarse, la dosis recomendada y el tiempo.En este TFG hemos estudiado la literatura científica más reciente sobre el tema concluyendo que la dieta es el factor con mayor influencia sobre la composición de la microbiota, aunque también se puede modificar mediante tratamientos como la TMF o el uso de probióticos y prebióticos. Cada individuo tendrá una respuesta diferente a los distintos macronutrientes y a la pérdida de peso en función de su enterotipo dominante. Factores como el mantenimiento de unos niveles de glucemia estables y un aporte adecuado de fibra alimentaria resultan beneficiosos tanto para la microbiota como para el sistema inmune.<br /

Síndrome de sobrecarga en cuidadores de Alzheimer. Revisión sistemática

El progresivo envejecimiento de la sociedad hace que se disparen los índices de enfermedades asociadas a la senectud como es el caso de la enfermedad de Alzheimer (EA), la cual produce un deterioro cognitivo progresivo generando gran dependencia a los afectados y cuyo cuidado suele recaer en un único cuidador, con frecuencia conllevado una gran carga de trabajo y un deterioro de su salud. La presente revisión sistemática tiene como objetivo profundizar en el conocimiento sobre los factores relacionados con la sobrecarga en cuidadores informales de EA. Los hallazgos derivados de los estudios confirman el predominio de las mujeres en las tareas relacionadas con el cuidado. También queda de manifiesto la presencia de altos niveles de carga en cuidadores de EA y la existencia de factores moderadores, como la resiliencia, las estrategias de afrontamiento, los aspectos positivos del cuidado, la religiosidad, la autoeficacia o el apoyo social percibido.The progressive aging of society causes the rates of diseases associated with senescence to skyrocket, such as Alzheimer’s disease (AD), which produces a progressive cognitive deterioration generating great dependence on those affected and whose care usually falls on a single caregiver, often with a heavy workload and deteriorating health. The objective of this systematic review is to deepen our understanding of the factors related to overload in informal caregivers of AD. The findings derived from the studies confirm the predominance of women in care-related tasks. The presence of high levels of burden on AD caregivers and the existence of moderating factors, such as resilience, coping strategies, positive aspects of care, religiosity, self-efficacy or perceived social support are also evident

Comparison between different multidimensional analytical systems for protein identification

Comunicaciones a congreso

The Role of the Tumor Microenvironment in the Development and Progression of Hepatocellular Carcinoma

There is a growing evidence that supports the role of the tumor microenvironment (TME) in the development and progression of cancer. TME is composed of cellular components, bioactive substances (e.g. growth factors) and extracellular matrix (ECM) comprising of proteins such as collagens, proteoglycans and the linear glycosaminoglycan hyaluronan, which is a key component of ECM. Hepatocellular carcinoma (HCC), generally arises from fibrotic or cirrhotic liver, characterized by excessive expression and alteration of ECM components which facilitates tumor development. On the other hand, non-tumoral cells, as such as the mesenchymal stem/stromal cells (MSCs) are typically recruited to the injured or hypoxic area within the tumor. Besides the secretion of immunoregulatory, growth factors and cytokines, MSCs and hepatic stellate cells (HSCs) can also synthesize hyaluronan, amongst other components, that affects several tumor processes. The TME also contains different types of immune cells. A key component in tumorigenesis in HCC are the macrophages, as tumor-associated macrophages (TAM). This chapter will describe specific data regarding the interaction of MSCs-hyaluronan-TAMs and tumor cells and how this interaction potentially contributes to the development and progression of HCC.Fil: Sevic, Ina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Spinelli, Fiorella Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Cantero, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Reszegi, Andrea. Semmelweis University; HungríaFil: Kovalszky, Ilona. Semmelweis University; HungríaFil: García, Mariana Gabriela. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentin

The effect of Galanin N-Terminal fragment (1-15) in anhedonia: Involvement of the dopaminergic mesolimbic system.

The Galanin N-terminal fragment (1-15) [GAL(1-15)] induces depressant- and anxiogenic-like actions in behavioral tests and these effects were significantly stronger than the ones induced by Galanin. Since anhedonia is a core feature of depression, we have analyzed GAL(1-15) actions in two anhedonic-like behavior tests: saccharin Self-administration and Sucrose Preference test (SPT). In order to investigate whether the effect of GAL(1–15) was associated with the reward circuit, we have studied the GAL(1-15) actions over the mesolimbic system by the expression of the C-Fos, Dat, Vmat2 and Dopamine and GAL receptors genes in VTA and NAc. GAL(1-15) 3nmol significantly decreased the number of reinforcement of saccharin self-administer (p<0.01), while 1nmol lacked effect. GAL(1-15) also significantly reduced the number of reinforcement (p<0.01) compared with GAL. The GALR2 antagonist M871 significantly blocked (p<0.05) the decrease in the number of saccharin reinforcements induced by GAL(1-15). In the SPT, GAL(1-15) decreased the sucrose intake 8 (p<0.05) and 24 hours (p<0.01) after administration. GAL(1-15) at a dose of 3 nmol produced a significant decrease in the mRNA levels of Dat and Vmat2 (p<0.05) and an increase in the D3 receptor (p<0.05) in VTA. In the NAc, GAL(1-15) induced a significant decrease in the expression of C-Fos (p<0.05) mRNA and a significantly increased the mRNA expression of D1 (p<0.05), D2 (p<0.05) and D3 (p<0.05). In the current study, we described for the first time that GAL(1-15) induced a strong anhedonia-like phenotype in several behavioral tests, confirming an important role of this neuropeptide in anhedonia, moreover, the dopaminergic mesolimbic system was described as a key region in GAL(1-15)-mediated action on anhedonia. These results may give the basis for the development of novel therapeutic strategies using GAL(1-15) for treatment of depression and reward-related diseases.This study was supported by SpanishSAF2016-79008 and PPIT.UMA.B1.2017/17. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Effects of galanin n-terminal fragment (1-15) in sac- charin self-administration and sucrose preference test in rats.

The Galanin N-terminal fragment (1-15) [GAL(1-15)] induces depressant- and anxiogenic- like actions in several behavioral tests, and these effects were significantly stronger than the ones induced by Galanin (1-29). Since, anhedonia is a core feature of major depressive disor- der, we have analyzed GAL(1-15) actions in two anhedonic-like behaviour tests: saccharin Self-administration and Sucrose Preference test. Three sets of experimemts were conducted in the saccharin Self-administration test. In the first, a dose-response curve of GAL(1-15) 1nmol, 3nmol or vehicle was performed. We have also compared the effects in the number of saccharine reinforcements of Galanin (1-29) 3nmol and GAL(1-15) 3nmol. In the last experiments, rats received i.c.v. GAL(1-15) 3nmol and the GALR2 antagonist M871 3nmol. In Sucrose Preference test, we have analyzed the effects of GAL(1-15) 3nmol in the sucrose intake and preference after 2, 8 and 24 h. GAL(1-15) 3nmol significantly decreased the number of reinforcement of saccharin self- administer (p<0.01), while 1nmol lacked effect. GAL(1-15) also significantly reduced the number of reinforcement (p<0.01) compared with Galanin (1-29). The GALR2 antagonist M871 significantly blocked (p<0.05) the decrease in the number of saccharin reinforcements administration induced by GAL(1-15). In the Sucrose Preference test, GAL(1-15) decreased the sucrose intake 8 (p<0.05) and 24 hours (p<0.01) after administration. In the current study, we described for the first time that GAL(1-15) induced a strong anhe- donia-like phenotype in the saccharin self-administration and Sucrose Preference test, con- firming an important role of this neuropeptide in anhedonia, a core feature of major depres- sive disorders.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This study was supported by Spanish SAF2016-79008-P and PPIT.UMA.B1.2017/17

Galanin N-terminal fragment (1− 15) reduces alcohol seeking and alcohol relapse in rats: Involvement of mesocorticolimbic system

Alcohol Use Disorder (AUD) is among the most prevalent mental illnesses, and due to the low efficacy of the current medication, it is essential to find new biological targets that could modulate alcohol consumption. Since Galanin (1− 15) [GAL(1− 15)] produces a loss of motivational behaviour by an artificial reinforcer and decreases the preference an alcohol consumption in a voluntary alcohol intake, we have studied the role of GAL(1− 15) in alcohol-seekingbehaviourandtheinvolvementofthecorticomesolimbicsystemaswellastheroleofGAL(1− 15) in context-induced alcohol relapse. In rats, we have studied GAL(1− 15)-effects on alcohol-seeking in self- administration, in fixed-ratio (FR1) and progressive-ratio (PR), and the involvement of GAL receptors using siRNA GALR1 or GALR2 knockdown animals. We have analysed the transcriptional changes of C-Fos, dopamine receptors, GAL receptors and 5HT1A receptors in the corticomesolimbic system. Also, we have examined the effect of GAL(1− 15) in context-induced alcohol relapse. GAL(1− 15) substantially reduced alcohol-seeking behaviour in the operant self-administration model in an FR1 protocol and at the breaking point in a PR schedule. GALR1and GALR2 were involved in these effects, as indicated by the analysis by GALR2 antagonist and GALR1 and GALR2 knockdown animals. Notably, the mechanism of GAL(1− 15)-mediated actions involved changes in C-Fos, Dopamine receptors and 5HT1A expression in the ventral tegmental area, accumbens nucleus and prefrontal cortex. Significantly, GAL(1− 15) reduced the context-induced alcohol relapse. These results open up the possibility to use GAL(1− 15) as a novel strategy in AUD.This work was supported by grants awarded by Spanish Ministry of Economy PID2020-114392RB-100, PDC2021-121566-100 and by Junta de Andalucía P20-00026-R and PI-0083-2019

The dopaminergic mesolimbic system are involved in the anhedonic-like effects produced by galanin (1-15) in rats.

Galanin (1-15)[GAL(1-15)] induces depressant- and anxiogenic-like actions in several behavioural tests. Recently, we described that GAL(1-15) induces an anhedonic-like effect in saccharine self-administration and sucrose preference test in rats. In order to investigate whether the effect of GAL(1–15) in anhedonia was associated with the reward circuit, we have studied the GAL(1-15) actions over the mesolimbic system by PET for in vivo imaging and in the expression of the C-Fos, Dat, Vmat2 and Dopamine and Galanin receptors genes in VTA and NAc. In the PET experiments, the [18F]FDG at 30, 60 and 90min after GAL(1-15) administration was measure as indicative of brain glucose metabolism. In the qPCR experiments, groups of rats (n=5-6) were killed 1h after i.c.v. GAL(1-15) 3nmol or vehicle. The VTA and NAc were dissected and the mRNA expression of C-Fos, Dat, Vmat2 and D1, D2, D3, D5, GALR1, and GALR2 receptors were measured by RT-qPCR. The GAL(1-15) induced a decrease in [18F]FDG uptake in the hippocampus and thalamus at 30, 60 and 90min, and in the striatum at 30min, however, in the prefrontal cortex, an increase in [18F]FDG uptake was observed after 30 and 60min. GAL(1-15) at a dose of 3 nmol produced a significant decrease in the mRNA levels of Dat and Vmat2 (p<0.05) and an increase in the D3 receptor (p<0.05) in VTA. In the NAc, GAL(1-15) induced a significant decrease in the expression of C-Fos (p<0.05) mRNA and a significantly increased the mRNA expression of D1 (p<0.05), D2 (p<0.05) and D3 (p<0.05). These results suggest the involvement of the dopaminergic mesolimbic system, a key region for the reward system, in GAL(1-15)-mediated action on anhedonia. These results may give the basis for the development of novel therapeutic strategies using GAL(1-15) for treatment of depression and reward-related diseases.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This study was supported by SpanishSAF2016-79008 and PPIT.UMA.B1.2017/17

Galanin (1-15) enhances the behavioural effects of escitalopram in the forced swimming test in rats

The selective serotonergic reuptake inhibitors (SSRIs) are the most commonly used for the treatment of major depression. Recently, we observed that the Galanin N-terminal fragment (1-15) [GAL(1-15)] enhances the antidepressant-like effects induced by Fluoxetine (FLX) in the forced swimming test (FST) (Flores-Burgess et al, 2017). Therefore, we have analyzed the ability of GAL(1-15) to enhance the behavioural effects of Escitalopram (ESC), other SSRIs, in the FST and the tail suspension test (TST). In the first set of experiments, groups of rats received three injections (23, 5 and 1 hour) before FST of two different doses of ESC (5mg/Kg or 7,5mg/Kg) or vehicle to perform a dose-response curve in the FST. Secondly, different groups of rats received three injections of ESC (7,5mg/Kg) and a single injection of a threshold dose of GAL(1-15) (1nmol) or aCSF 15 minutes before the FST and TST. In the dose-response curve, ESC 5 mg/kg and 7,5 mg/kg significantly increase the swimming time (p<0.05), while lacking effects over immobility time. The threshold dose of GAL(1-15) 1nmol enhanced the antidepressant-like effects mediated by ESC 7,5mg/Kg, decreasing the immobility (p<0.05) and increasing the swimming time (p<0.05) in the FST. In TST, no differences were found between the treatments. Our results indicate an interaction between GAL(1-15) and ESC in the FST and open up the possibility to use GAL(1-15) for a combination therapy with SSRIs as a depression treatment.This study was supported by Spanish SAF2016-79008-P, PI-0083-2019 and UMA18-FEDERJA-008 Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech