Metabolomics and biochemical alterations caused by pleiotrophin in the 6‑hydroxydopamine mouse model of Parkinson’s disease.

Pleiotrophin (PTN) is a cytokine involved in nerve tissue repair processes, neuroinflammation and neuronal survival. PTN expression levels are upregulated in the nigrostriatal pathway of Parkinson’s Disease (PD) patients. We aimed to characterize the dopaminergic injury and glial responses in the nigrostriatal pathway of mice with transgenic Ptn overexpression in the brain (Ptn-Tg) after intrastriatal injection of the catecholaminergic toxic 6-hydroxydopamine (6-OHDA) at a low dose (5 µg). Ten days after surgery, the injection of 6-OHDA induced a significant decrease of the number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra and of the striatal TH contents in Wild type (Wt) mice. In contrast, these effects of 6-OHDA were absent in Ptn-Tg mice. When the striatal Iba1 and GFAP immunoreactivity was studied, no statistical differences were found between vehicle-injected Wt and Ptn-Tg mice. Furthermore, 6-OHDA did not cause robust glial responses neither on Wt or Ptn-Tg mice 10 days after injections. In metabolomics studies, we detected interesting metabolites that significantly discriminate the more injured 6-OHDA-injected Wt striatum and the more protected 6-OHDA-injected Ptn-Tg striatum. Particularly, we detected groups of metabolites, mostly corresponding to phospholipids, whose trends were opposite in both groups. In summary, the data confirm lower 6-OHDA-induced decreases of TH contents in the nigrostriatal pathway of Ptn-Tg mice, suggesting a neuroprotective effect of brain PTN overexpression in this mouse model of PD. New lipid-related PD drug candidates emerge from this study and the data presented here support the increasingly recognized “lipid cascade” in PD.post-print2513 K

Pleiotrophin overexpression regulates amphetamine-induced reward and striatal dopaminergic denervation without changing the expression of dopamine D1 and D2 receptors: Implications for neuroinflammation.

It was previously shown that mice with genetic deletion of the neurotrophic factor pleiotrophin (PTN-/-) show enhanced amphetamine neurotoxicity and impair extinction of amphetamine conditioned place preference (CPP), suggesting a modulatory role of PTN in amphetamine neurotoxicity and reward. We have now studied the effects of amphetamine (10mg/kg, 4 times, every 2h) in the striatum of mice with transgenic PTN overexpression (PTN-Tg) in the brain and in wild type (WT) mice. Amphetamine caused an enhanced loss of striatal dopaminergic terminals, together with a highly significant aggravation of amphetamine-induced increase in the number of GFAP-positive astrocytes, in the striatum of PTN-Tg mice compared to WT mice. Given the known contribution of D1 and D2 dopamine receptors to the neurotoxic effects of amphetamine, we also performed quantitative receptor autoradiography of both receptors in the brains of PTN-Tg and WT mice. D1 and D2 receptors binding in the striatum and other regions of interest was not altered by genotype or treatment. Finally, we found that amphetamine CPP was significantly reduced in PTN-Tg mice. The data demonstrate that PTN overexpression in the brain blocks the conditioning effects of amphetamine and enhances the characteristic striatal dopaminergic denervation caused by this drug. These results indicate for the first time deleterious effects of PTN in vivo by mechanisms that are probably independent of changes in the expression of D1 and D2 dopamine receptors. The data also suggest that PTN-induced neuroinflammation could be involved in the enhanced neurotoxic effects of amphetamine in the striatum of PTN-Tg mice

Estudio y desarrollo sobre sistemas de simulación para comunicaciones móviles, LTE

Este proyecto, recoge el estudio de diferentes simuladores sobre comunicaciones móviles, que se encargan de analizar el comportamiento de las tecnologías UMTS (Universal Mobile Telecommunications System), 3G y LTE (Long Term Evolution),3.9G, centrándose principalmente en el caso de los simuladores LTE, ya que es la tecnología que se está implantando en la actualidad. Por ello, antes de analizar las características de la interfaz radio más importante de esta generación, la 3.9G, se hará una overview general de cómo han ido evolucionando las comunicaciones móviles a lo largo de la historia, se analizarán las características de la tecnología móvil actual, la 3.9G, para posteriormente centrarse en un par de simuladores que demostrarán, mediante resultados gráficos, estas características. Hoy en día, el uso de estos simuladores es totalmente necesario, ya que las comunicaciones móviles, avanzan a un ritmo vertiginoso y es necesario por lo tanto conocer las prestaciones que pueden producir las diferentes tecnologías móviles utilizadas. Los simuladores utilizados por este proyecto, permiten analizar el comportamiento de varios escenarios, ya que existen diferentes tipos de simuladores, tanto a nivel de enlace como a nivel de sistema. Se mencionarán una serie de simuladores correspondientes a la tercera generación UMTS, pero los simuladores en cuestión que se estudiarán y analizarán con más profundidad en este proyecto fin de carrera son los simuladores “Link-Level” y “System-Level”, desarrollados por el “Institute of Communications and Radio-Frecuency Engineering” de la Universidad de Viena. Estos simuladores permiten realizar diferentes simulaciones, como analizar el comportamiento entre una estación base y un único usuario, para el caso de los simuladores a nivel de enlace, o bien analizar el comportamiento de toda una red en el caso de los simuladores a nivel de sistema. Con los resultados que se pueden obtener de ambos simuladores, se realizarán una serie de preguntas, basadas en la práctica realizada por el profesor de la universidad Politécnica de Madrid, Pedro García del Pino, tanto de tipo teóricas como de tipo prácticas, para comprobar que se han entendido los simuladores analizados. Finalmente se citarán las conclusiones que se obtiene de este proyecto, así como las líneas futuras de acción. PROJECT ABSTRACT This project includes the study of different simulators on mobile communications, which are responsible for analyzing the behavior of UMTS (Universal Mobile Telecommunications System), 3G and LTE (Long Term Evolution), 3.9G, mainly focusing on the case of LTE simulators because it is the technology that is being implemented today. Therefore, before analyzing the characteristics of the most important radio interface of this generation, 3.9G, there will give a general overview how the mobile communications have evolved throughout history, analyzing the characteristics of current mobile technology, the 3.9G, later focus on a pair of simulators that demonstrate through graphical results, these characteristics. Today, the use of these simulators is absolutely necessary, because mobile communications advance at a high rate, and it is necessary to know the features that can produce different mobile technologies that are used. The simulators used for this project, allow to analyze the behavior of several scenarios, as there are different types of simulators, both link and system level. It mentioned a number of simulators for the third generation UMTS, but the simulators in question to be studied and analyzed in this final project are the simulators "Link-Level" and "System-Level", developed by the "Institute of Communications and Radio-Frequency Engineering" at the University of Vienna. These simulators allow realize different simulations, analyze the behavior between a base station and a single user, in the case of the link-level simulators or analyze the performance of a network in the case of system-level simulators. With the results that can be obtained from both simulators, will perform a series of questions, based on the practice developed by Pedro García del Pino, Professor of “Universidad Politécnica de Madrid (UPM)”. These questions will be both of a theoretical and practical type, to check that have been understood the analyzed simulators. Finally, it quotes the conclusions obtained from this project and mention the future lines of action

Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine

Midkine (MK) is a cytokine that modulates amphetamine-induced striatal astrogliosis, suggesting a possible role of MK in neuroinflammation induced by amphetamine. To test this hypothesis, we studied astrogliosis and microglial response induced by amphetamine (10 mg/kg i.p. four times, every 2 h) in different brain areas of MK−/− mice and wild type (WT) mice. We found that amphetamine-induced microgliosis and astrocytosis are enhanced in the striatum of MK−/− mice in a region-specific manner. Surprisingly, LPS-induced astrogliosis in the striatum was blocked in MK−/− mice. Since striatal neuroinflammation induced by amphetamine-type stimulants correlates with the cognitive deficits induced by these drugs, we also tested the long-term effects of periadolescent amphetamine treatment (3 mg/kg i.p. daily for 10 days) in a memory task in MK−/− and WT mice. Significant deficits in the Y-maze test were only observed in amphetamine-pretreated MK−/− mice. The data demonstrate for the first time that MK is a novel modulator of neuroinflammation depending on the inflammatory stimulus and the brain area considered. The data indicate that MK limits amphetamine-induced striatal neuroinflammation. In addition, our data demonstrate that periadolescent amphetamine treatment in mice results in transient disruption of learning and memory processes in absence of endogenous MK

Perfil psicopatológico y de personalidad en dolor crónico no oncológico nociceptivo y neuropático: Estudio transversal comparativo

Introduction: Adaptation to chronic non-oncologic pain is associated with the development of psychopathology and personality disorders, creating severity, chronicity, poorer treatment response, and exacerbations in patients with neuropathy. Objective: To identify the psychopathological and personality profiles of patients with chronic nociceptive and neuropathic pain and their association with pain progression and intensity. Method: A cross-sectional, descriptive and comparative study was conducted in the Pain Treatment Unit of Hospital Universitari Sagrat Cor, with systematic randomized recruitment for 25 months; 115 patients were evaluated using the Hamilton Depression and Anxiety Rating Scale (HAM-D, HAM-A) and the Millon Clinical Multiaxial Inventory-III (MCMI-III). Results: The neuropathic group achieved significantly higher scores for pain intensity and depressive and anxiety symptoms. With greater magnitude and frequency, the neuropathic group related pain intensity and progression with depressive/anxiety symptoms, clinical syndromes, and personality patterns. Both groups revealed tendencies towards a compulsive personality pattern, followed by narcissistic, histrionic, and schizoid patterns. Conclusions: When treating chronic pain, the presence of various psychopathological indicators requires an individualized strategy.Introducción: La adaptación al dolor crónico no oncológico se asocia al desarrollo de psicopatología y afectaciones de la personalidad, generando severidad, cronicidad, menor respuesta al tratamiento y agravándose ante la neuropatía. Objetivo: Identificar perfiles psicopatológicos y de personalidad en pacientes con dolor crónico nociceptivo y neuropático, y su relación con la evolución e intensidad del dolor. Método: Estudio transversal, descriptivo y comparativo, realizado en la Unidad de Tratamiento del Dolor del Hospital Universitari Sagrat Cor, con reclutamiento aleatorio sistemático durante 25 meses; 115 pacientes fueron evaluados mediante la Escala de Hamilton para la Depresión y Ansiedad (HAM-D, HAM-A) y el Inventario Clínico Multiaxial de Millon III (MCMI-III). Resultados: El grupo neuropático obtuvo puntuaciones significativamente mayores en intensidad del dolor, sintomatología depresiva y ansiosa. Con más magnitud y frecuencia, relacionó la intensidad y evolución del dolor con sintomatología depresiva, ansiosa, síndromes clínicos y patrones de la personalidad. Ambos grupos revelaron tendencia al patrón de personalidad compulsiva, seguido del narcisista, histriónico y esquizoide. Conclusiones: En el tratamiento del dolor crónico, la presencia de distintos indicadores psicopatológicos requiere una estrategia individualizada