Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia

Overexpression of the mammalian homolog of the unc-18 gene (munc18-1) has been described in the brain of subjects with schizophrenia. Munc18-1 protein is involved in membrane fusion processes, exocytosis and neurotransmitter release. A transgenic mouse strain that overexpresses the protein isoform munc18-1a in the brain was characterized. This animal displays several schizophrenia-related behaviors, supersensitivity to hallucinogenic drugs and deficits in prepulse inhibition that reverse after antipsychotic treatment. Relevant brain areas (that is, cortex and striatum) exhibit reduced expression of dopamine D-1 receptors and dopamine transporters together with enhanced amphetamine-induced in vivo dopamine release. Magnetic resonance imaging demonstrates decreased gray matter volume in the transgenic animal. In conclusion, the mouse overexpressing brain munc18-1a represents a new valid animal model that resembles functional and structural abnormalities in patients with schizophrenia.

Cytokine pathway disruption in a mouse model of schizophrenia induced by Munc18-1a overexpression in the brain

Background: An accumulating body of evidence points to the significance of neuroinflammation and immunogenetics in schizophrenia, and an imbalance of cytokines in the central nervous system (CNS) has been suggested to be associated with the disorder. Munc18-overexpressing mice (Munc18-OE) have provided a model for the study of the alterations that may underlie the symptoms of subjects with schizophrenia. The aim of the present study was to elucidate the involvement of neuroinflammation and cytokine imbalance in this model. Methods: Cytokines were evaluated in the cortex and the striatum of Munc18-OE and wild-type (WT) mice by enzyme-linked immunosorbent assay (ELISA). Protein levels of specific microglia and macrophage, astrocytic and neuroinflammation markers were quantified by western blot in the cortex and the striatum of Munc18-OE and WT mice. Results: Each cytokine evaluated (Interferon-gamma (IFN-gamma), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-2 (IL-2) and CCL2 chemokine) was present at higher levels in the striatum of Munc18-OE mice than WT. Cortical TNF-alpha and IL-2 levels were significantly lower in Munc18-OE mice than WT mice. The microglia and macrophage marker CD11b was lower in the cortexes of Munc18-OE mice than WT, but no differences were observed in the striatum. Glial Fibrillary Acidic Protein (GFAP) and Nuclear Factor-kappaB (NF-kappa B)p65 levels were not different between the groups. Interleukin-1beta (IL-1 beta) and IL-6 levels were beneath detection limits. Conclusions: The disrupted levels of cytokines detected in the brain of Munc18-OE mice was found to be similar to clinical reports and endorses study of this type for analysis of this aspect of the disorder. The lower CD11b expression in the cortex but not in the striatum of the Munc18-OE mice may reflect differences in physiological activity. The cytokine expression pattern observed in Munc18-OE mice is similar to a previously published model of schizophrenia caused by maternal immune activation. Together, these data suggest a possible role for an immune imbalance in this disorder.

Taller Integrado 1A (Proyectos I, Dibujo Arquitectónico I, Análisis Constructivo I)

Nivel educativo: Grado. Duración (en horas): De 41 a 50 horas

Identification of a biomarker panel for colorectal cancer diagnosis

Background: Malignancies arising in the large bowel cause the second largest number of deaths from cancer in the Western World. Despite progresses made during the last decades, colorectal cancer remains one of the most frequent and deadly neoplasias in the western countries. Methods: A genomic study of human colorectal cancer has been carried out on a total of 31 tumoral samples, corresponding to different stages of the disease, and 33 non-tumoral samples. The study was carried out by hybridisation of the tumour samples against a reference pool of non-tumoral samples using Agilent Human 1A 60- mer oligo microarrays. The results obtained were validated by qRT-PCR. In the subsequent bioinformatics analysis, gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling were built. The consensus among all the induced models produced a hierarchy of dependences and, thus, of variables. Results: After an exhaustive process of pre-processing to ensure data quality–lost values imputation, probes quality, data smoothing and intraclass variability filtering–the final dataset comprised a total of 8, 104 probes. Next, a supervised classification approach and data analysis was carried out to obtain the most relevant genes. Two of them are directly involved in cancer progression and in particular in colorectal cancer. Finally, a supervised classifier was induced to classify new unseen samples. Conclusions: We have developed a tentative model for the diagnosis of colorectal cancer based on a biomarker panel. Our results indicate that the gene profile described herein can discriminate between non-cancerous and cancerous samples with 94.45% accuracy using different supervised classifiers (AUC values in the range of 0.997 and 0.955).

Las contribuciones vascas a la Hacienda Real en la Edad Moderna: Algunos contrastes provinciales

[ES]Este artículo tiene un doble objetivo. E1 primero, ofrecer una panorámica general sobre las contribuciones fiscales de las Provincias Vascas a la Corona durante el Antiguo Régimen,resaltando las diferencias que en ese orden existían entre las tres.El segundo,situar las demandas fiscales regias en el origen de las haciendas provinciales vascas,estableciendo los distintos ritmos que se siguieron en su conformación entre los siglos XVII y XVIII, hasta alcanzar una mayor homologación ya en 1a centuria siguiente.

Regulación alfa1-adrenérgica de la corriente IKr cardiaca

149 p. : il., graf.

Interpretación litoestratigráfica y paleogeográfica del Jurásico marino del este Cantabria-oeste de Vizcaya en base a diagrafías de sondeo y su correlación con series tipo

Este trabajo se centra en el estudio del Jurásico marino (Lías y Dogger) de un área de la parte central de La Cuenca Vasco-Cantábrica situada en el este de Cantabria y oeste de Vizcaya donde sus afloramientos son muy escasos pero se dispone de datos de sondeos de exploración petrolífera (Fig 1A y B), poniendo especial interés en la localización y distribución lateral de los niveles de rocas madre de hidrocarburos (black shales) y de potenciales almacenes (unidades carbonatadas fracturadas o dolomitizadas). La sucesión del Jurásico de la Cuenca Vasco-Cantábrica (CVC) está formada por dos unidades diferenciadas por edad y ambiente sedimentario. Por una parte tenemos los materiales del “Jurásico marino” (Robles et al., 1989) que representan la mayor parte de la sucesión (Lías y Dogger) y por otro lado, tenemos los materiales del “Jurásico continental” pertenecientes exclusivamente al Tithoniense Superior y que se engloban en las facies Purbeck que abarcan hasta el Berriasiense (Rat 1962).

Caracterización de las proteínas del complejo SNARE en esquizofrenia y su tratamiento

248 p.