Central nervous system gene expression changes in a transgenic mouse model for bovine spongiform encephalopathy.

Gene expression analysis has proven to be a very useful tool to gain knowledge of the factors involved in the pathogenesis of diseases, particularly in the initial or preclinical stages. With the aim of finding new data on the events occurring in the Central Nervous System in animals affected with Bovine Spongiform Encephalopathy, a comprehensive genome wide gene expression study was conducted at different time points of the disease on mice genetically modified to model the bovine species brain in terms of cellular prion protein. An accurate analysis of the information generated by microarray technique was the key point to assess the biological relevance of the data obtained in terms of Transmissible Spongiform Encephalopathy pathogenesis. Validation of the microarray technique was achieved by RT-PCR confirming the RNA change and immunohistochemistry techniques that verified that expression changes were translated into variable levels of protein for selected genes. Our study reveals changes in the expression of genes, some of them not previously associated with prion diseases, at early stages of the disease previous to the detection of the pathological prion protein, that might have a role in neuronal degeneration and several transcriptional changes showing an important imbalance in the Central Nervous System homeostasis in advanced stages of the disease. Genes whose expression is altered at early stages of the disease should be considered as possible therapeutic targets and potential disease markers in preclinical diagnostic tool development. Genes non-previously related to prion diseases should be taken into consideration for further investigations.

[Repeated measures analysis]. / Análisis de medidas repetidas.

In this chapter we present the most frequent statistical methods used on the repeated measures analysis, putting emphasis on the different types of data and the limitation of each method. The main objective consists in giving a comparison of the different methods from a practical point of view and with a medical perspective. For each approach we give a brief mathematical introduction, a discussion about the conditions for its application suggesting what kind of data are appropriated and, finally, it is illustrated by the study of the analysis of some data sets including a brief discussion of the results.

Análisis de medidas repetidas / Repeated measures analysis

En este trabajo se realiza una exposición de los métodos estadísticos que se utilizan más frecuentemente en el análisis de medidas repetidas, haciendo énfasis en el tipo de datos y las limitaciones de cada método. El objetivo principal consiste en dar una visión comparativa de los distintos métodos desde un punto de vista práctico en el entorno de aplicaciones médicas. Para cada una de las aproximaciones se plantea una breve introducción matemática, una discusión de las condiciones de aplicación que permiten tener una idea del tipo de diseños en los que se puede utilizar y, finalmente, el análisis de unos datos concretos con una breve discusión de resultados (AU)