Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model : mechanism for deficient glutamatergic transmission?

Astrocytes are fundamental for brain homeostasis and the progression and outcome of many neuropathologies including Alzheimer's disease (AD). In the triple transgenic mouse model of AD (3xTg-AD) generalised hippocampal astroglia atrophy precedes a restricted and specific beta-amyloid (A beta) plaque-related astrogliosis. Astrocytes are critical for CNS glutamatergic transmission being the principal elements of glutamate homeostasis through maintaining its synthesis, uptake and turnover via glutamate-glutamine shuttle. Glutamine synthetase (GS), which is specifically expressed in astrocytes, forms glutamine by an ATP-dependent amination of glutamate. Here, we report changes in GS astrocytic expression in two major cognitive areas of the hippocampus (the dentate gyrus, DG and the CA1) in 3xTg-AD animals aged between 9 and 18 months. We found a significant reduction in Nv (number of cell/mm(3)) of GS immunoreactive (GS-IR) astrocytes starting from 12 months (28.59%) of age in the DG, and sustained at 18 months (31.65%). CA1 decrease of GS-positive astrocytes Nv (33.26%) occurs at 18 months. This Nv reduction of GSIR astrocytes is paralleled by a decrease in overall GS expression (determined by its optical density) that becomes significant at 18 months (21.61% and 19.68% in DG and CA1, respectively). GS-IR Nv changes are directly associated with the presence of A beta deposits showing a decrease of 47.92% as opposed to 23.47% in areas free of A beta. These changes in GS containing astrocytes and GS-immunoreactivity indicate AD-related impairments of glutamate homeostatic system, at the advanced and late stages of the disease, which may affect the efficacy of glutamatergic transmission in the diseased brain that may contribute to the cognitive deficiency.

Early astrocytic atrophy in the entorhinal cortex of a triple transgenic animal model of Alzheimer's disease

The EC (entorhinal cortex) is fundamental for cognitive and mnesic functions. Thus damage to this area appears as a key element in the progression of AD (Alzheimer's disease), resulting in memory deficits arising from neuronal and synaptic alterations as well as glial malfunction. In this paper, we have performed an in-depth analysis of astroglial morphology in the EC by measuring the surface and volume of the GFAP (glial fibrillary acidic protein) profiles in a triple transgenic mouse model of AD [3xTg-AD (triple transgenic mice of AD)]. We found significant reduction in both the surface and volume of GFAP-labelled profiles in 3xTg-AD animals from very early ages (1 month) when compared with non-Tg (non-transgenic) controls (48 and 54%, reduction respectively), which was sustained for up to 12 months (33 and 45% reduction respectively). The appearance of Lambda beta (amyloid beta-peptide) depositions at 12 months of age did not trigger astroglial hypertrophy; nor did it result in the close association of astrocytes with senile plaques. Our results suggest that the AD progressive cognitive deterioration can be associated with an early reduction of astrocytic arborization and shrinkage of the astroglial domain, which may affect synaptic connectivity within the EC and between the EC and other brain regions. In addition, the EC seems to be particularly vulnerable to AD pathology because of the absence of evident astrogliosis in response to A beta accumulation. Thus we can consider that targeting astroglial atrophy may represent a therapeutic strategy which might slow down the progression of AD.

The Equivalency Principle for Discounting the Value of Natural Assets: An Application to an Investment Project in the Basque Coast

25 p.

Análisis de la fabricación de las tijas de una motocicleta de competición. Prototipo

[ES]Este trabajo fin de grado, TFG en adelante, consiste en el análisis de la fabricación de las tijas de una motocicleta de competición Motostudent. Se trata de conseguir fabricar las tijas de una manera óptima, tanto en que su material como el proceso de fabricación sea el más adecuado para su función siendo, además, lo más económico posible. Para llevar a cabo este trabajo es necesario conocer las cualidades que una tija debe cubrir en una motocicleta de competición. A partir de dichas cualidades se selecciona el material idóneo de entre otros muchos, estudiando las propiedades fiscas, químicas y mecánicas de cada uno de ellos. También se hará un estudio de dos alternativas de fabricación posibles, electroerosión y arranque de viruta con herramienta, para a posteriori elegir la más indicada. La idea no es construir un diseño final para la fabricación, sino un prototipo sobre el cual hacer las pruebas oportunas y posteriormente realizar cambios y mejoras para posteriores ediciones. El presente proyecto marcará las pautas de diseño y el proceso a seguir durante la fabricación de las tijas que el equipo representante de la Escuela técnica superior de Bilbao, ETSIB en adelante, empleará en la futura competición.

Optimisation of the first principle code Octopus for massive parallel architectures: application to light harvesting complexes

150 p.

Utilización del Modelo de Triple Hélice para el desarrollo de nuevos sectores productivos en el contexto de la Industria 4.0

Máster en Dirección Empresarial desde la Innovación y la Internacionalización. Curso 2014/2015

Spin squeezing, macrorealism and the heisenberg uncertainty principle

169 p.