Anàlisi transcripcional global durant el desenvolupament d'encefalopaties espongiformes transmissibles

The aim of this project is to contribute to the knowledge of the pathogeny of the Bovine Spongiform Ecephalopathy (BSE), comparing it to studies performed on other species and in the human beings, accessing how prions once the tonsil epithelium and the intestinal barrier are crossed, gain access to the nervous tissue in the gastrointestinal tract (Enteric Nervous System, ENS), which dissemination pathways and cellular elements are used to finally reach the Central Nervous System (ANS), and also, the changes induced in those systems. With this purpose we will characterize the lesional pattern produced by such disease in a murine model, using transgenic mice expressing the bovine PrP gene inoculated with the BSE causative agent. We will as well study the cellular changes involved in the establishment of the morphological and clinical changes which characterize BSE. The involvement of the nervous pathways in the process of "neuroinvasion"will also be assessed: diffusion of prions from the gastrointestinal tract to the CNS, determining which cellular elements and chemical mediators are involved in such process. Particularly, the CNS will be studied focusing on the changes affecting neurons (cell death and neuronal loss, changes in the ctytoskeleton and axonal transport systems, synaptic proteins), the extracellular matrix, the role of glial cells and changes related to cellular stress which can alter such elements of the nervous tissue. Finally, we will also study the possible altered gene expression as a consequence of BSE and its paper in the disease; to understand the TSEs pathogeny, target genes will the ones involved in neuronal death processes, glial proliferation phenomena, and also genes related to the energetic metabolism, signal transduction cascades and transcriptions mechanisms