Objective
Transmissible Spongiform Encephalopathies, or Prion diseases, are a group of slow and deadly degenerative pathologies of the Central Nervous System affecting not only animals but also humans. They encompass mainly Creutzfeldt-Jakob disease in man, scrapie in sheep and goat and bovine spongiform encephalopathy. One of the least known aspects of these rare pathologies is the sequence of events triggered by the conformational change of PrPc into PrPsc, and leading to neuropathological degeneration. The present proposal is specifically designed to address this central problem, by a collaborative approach between four European laboratories with strong expertise in molecular biological, morphological and electrophysiological techniques. We feel that a global approach, integrating the specific data obtained by each of these techniques in a unified view, is the only way to get an efficient cross-talk and a rapid progress in the understanding of these puzzling pathologies.
We have chosen to concentrate on the study of two specific and related problems: 1 - what is the role of PrPc in normal neurons, glia and neural circuits? and 2 - what are the structural changes leading to the morpho-functional alterations of prion-infected CNS structures? The cerebellum was taken as a model structure to study the normal and pathological aspects of PrP because it is one of the best known brain parts, which insures a rapid and precise integration of new data in a coherent body of biological relationships and because there is a significant cerebellar tropism of PrP physiopathology.
Single cell RT-PCR, Golgi impregnation and immunohistochemical labelling, photon and electron-microscopical analysis and electrophysiological recordings in normal, in PrP0/0 and in scrapie-infected murine strains will be used to address the two above-mentioned problems. The experimental approach has been divided in four packages and fourteen activities, each to be achieved in a specific time inside the three year program. The main goals consist of 1 )PrPc localization on cellular types of normal cerebellum. 2) Analysis of the cortico-cerebellar network of PrP0/0 mice 3) Determination of the exact time table of degeneration in scrapie-inoculated strains. 4) Determination of structural mechanisms responsible for cell degeneration.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- medical and health sciences basic medicine pathology
- natural sciences physical sciences theoretical physics particle physics photons
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Coordinator
75634 Paris
France
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