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Gonadal hormone deprivation (GHD) and decline such as menopause and bilateral oophorectomy are associated with an increased risk of neurodegeneration. Yet, hormone therapies (HTs) show varying efficacy, influenced by factors such as sex, drug type, and timing of treatment relative to hormone decline. We hypothesize that the molecular environment of the brain undergoes a transition following GHD, impacting the effectiveness of HTs. Using a GHD model in mice treated with Tibolone, we conducted proteomic analysis and identified a reprogrammed response to Tibolone, a compound that stimulates estrogenic, progestogenic, and androgenic pathways. Through a comprehensive network pharmacological workflow, we identified a reprogrammed response to Tibolone, particularly within "Pathways of Neurodegeneration", as well as interconnected pathways including "cellular respiration", "carbon metabolism", and "cellular homeostasis". Analysis revealed 23 proteins whose Tibolone response depended on GHD and/or sex, implicating critical processes like oxidative phosphorylation and calcium signalling. Our findings suggest the therapeutic efficacy of HTs may depend on these variables, suggesting a need for greater precision medicine considerations whilst highlighting the need to uncover underlying mechanisms.

Ovarian hormones exert anti-depressive and anxiolytic actions. In this study we have analyzed the effects of ovariectomy on the development of anxiety and depression-like behaviors and on cell proliferation in the hippocampus of mice submitted to chronic unpredictable stress. Animals submitted to stress 4 months after ovariectomy showed a significant increase in immobility behavior in the forced swimming test compared to animals submitted to stress 2 weeks after ovariectomy. In addition, long-term ovariectomy resulted in a significant decrease on the time spent in the open arms in the elevated plus-maze test compared to control animals. Stress did not significantly affect cell proliferation in the hilus of the dentate gyrus. However, ovariectomy resulted in a significant decrease in cell proliferation. These results indicate that long-term deprivation of ovarian hormones enhances the effect of chronic unpredictable stress on depressive- and anxiety-like behaviors in mice. Therefore, a prolonged deprivation of ovarian hormones may represent a risk factor for the development of depressive and anxiety symptoms after the exposure to stressful experiences., Depto. de Medicina Legal, Psiquiatría y Patología, Fac. de Medicina, TRUE, pub

Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations., Depto. de Medicina Legal, Psiquiatría y Patología, Fac. de Medicina, TRUE, pub

Los microplásticos son partículas de un tamaño inferior a 5 milímetros que han emergido como una creciente preocupación en los ecosistemas acuáticos a nivel global. Su presencia generalizada y persistencia en ambientes marinos ha despertado una alarma ambiental debido a su impacto negativo en la vida marina, la salud humana y el bienestar de los ecosistemas en su conjunto. La acumulación de microplásticos en los océanos representa un desafío, ya que pueden ser ingeridos por organismos acuáticos y potencialmente ingresar a la cadena alimentaria, con consecuencias aún por determinar. Por estos motivos, la detección y cuantificación de estas partículas se ha convertido en un objetivo crucial. Para este fin se han propuesto diferentes métodos como la espectroscopía infrarroja o las imágenes hiperespectrales. En este proyecto fin de Máster se va a estudiar la idoneidad del uso de dispersión de ultrasonidos o backscattering ultrasónico de alta frecuencia para la detección de microplásticos en el entorno marino. Este estudio comprende: la revisión de antecedentes y avances en este campo; la búsqueda de un modelo teórico que sirva de base y que permita comprender las variables significativas que determinan la capacidad de esta técnica para identificar micropartículas de diferente naturaleza así como analizar los resultados obtenidos y; por último, de una fase experimental para evaluar la viabilidad real del método, en la que se han empleado suspensiones de partículas de poliestireno y levaduras en un rango de tamaños 7-10um, como modelos de dispersores plásticos y orgánicos, respectivamente. En esta última fase se caracterizan las partículas de manera óptica y acústica. El análisis óptico se realiza en laboratorio mediante un microscopio y el programa de procesamiento de imágenes ImageJ. El análisis acústico comienza con la obtención de imágenes ultrasónicas y procesado de las mismas, y termina con una clasificación de las partículas detectadas a partir de algoritmos desarr, [ENG] Microplastics are microparticles smaller than 5 millimetres in size that have emerged as a growing concern in aquatic ecosystems globally. Their widespread presence and persistence in marine environments have raised environmental alarm due to their negative impact on marine life, human health, and the welfare of ecosystems. The accumulation of microplastics in the oceans represents a challenge, as they can be ingested by aquatic organisms and potentially reach the food chain, with consequences yet to be determined. For these reasons, detection and quantification of these particles has become a crucial objective. For this end, different methods have been suggested, such as infrared spectroscopy or hyperspectral imaging. This master’s final project will study the suitability of the use of ultrasound scattering or high- frequency ultrasonic backscattering for the detection of microplastics in the marine environment. This study includes: a review of the background and advances in this field the search for a theoretical model to serve as a basis for understanding the significant variables that determine the capacity of this technique to identify microparticles of different natures and to analyse the results obtained; and finally, an experimental phase to evaluate the real viability of the method, in which suspensions of polystyrene and yeast particles in a size range of 7-10um have been used as models of plastic and organic dispersants, respectively. In this last phase, the particles are characterised optically and acoustically. The optical analysis is performed in the laboratory using a microscope and the image processing software ImageJ. The acoustic analysis begins with the acquisition of ultrasonic images and their processing and ends with a classification of the detected particles based on algorithms developed throughout this work and implemented in the Matlab programming platform. The results obtained in this preliminary study are promising. After evaluating

En este trabajo de fin de máster se aborda el diseño de un algoritmo para el cálculo de la velocidad del flujo sanguíneo dentro de pequeños vasos a través de técnicas ecográficas, su implementación en Matlab y un estudio de su funcionamiento. El tema ha sido propuesto por el CSIC/ITEFI (Consejo Superior de Investigaciones Científicas/ Instituto de Tecnologías Físicas y de la Información), y ha sido tutorizado por Luis Elvira Segura y por María Luisa Rapún Banzo, del CSIC y de la UPM respectivamente. Se presentarán en este apartado los motivos para la elaboración de este proyecto, un contexto para poder situar el tema a trabajar en un nivel teórico y tecnológico y un pequeño resumen de cómo se organiza esta memoria.