NR ATPB
AU Faucheux,B.A.; Privat,N.; Laffont-Proust,I.; Sazdovitch,V.; Matos,A.; Brandel,J.P.; Maurage,C.A.; Laplanche,J.L.; Hauw,J.J.; Haik,S.
TI Is microglial activation significantly correlated to PrPres deposits and neuronal loss in the brain of patients with sporadic Creutzfeldt-Jakob disease?
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Pathogenesis PATH-12
PT Konferenz-Poster
AB
The mechanisms involved in neurodegeneration are still poorly understood in human prion diseases, although neuronal death is a central component of the neuropathological pattern. Neurodegeneration varies according to the forms of the disease, brain regions and neuronal populations. Neurons of the granule cell layer of the cerebellum are severely depleted in some cases of sporadic Creutzfeldt-Jakob disease. Microglial cells and PrPsc toxicity have been proposed to play a central role in the degeneration of neurons in transmissible spongiform encephalopathies. We therefore investigated microglial cells and neuronal density in a definite brain region and studied their relationships with PrPres accumulation. In the cerebellum of patients with sporadic Creutzfeldt-Jakob disease (n=85) and matched controls (n=30), we quantified the density of these cells (estimated with a computer-assisted image analysis system) and some markers of neurodegeneration and neuropathological lesions (spongiosis, gliosis). Activated microglia was detected after immuno-histochemistry. We studied the location and patterns of the prion protein deposits as shown by immuno-histochemistry of tissue sections, the biochemical characteristics of proteinase K resistant prion protein (PrPres type) present in the cerebellum as determined by Western blotting of tissue homogenates, and the polymorphism at codon 129 of the PRNP gene as deduced from genomic DNA sequencing. Our findings clearly demonstrate in humans a positive correlation between the number of microglial cells and the amount of PrPres present in the cerebellum, as well as relationships between neuronal loss, microglial activation and the amount of PrPres.
This work was carried out with the support of grants from GIS 'Infections à prions' (F127) and INSERM-ATC 'Prions'.
AD B.A.Faucheux, N.Privat, I.Laffont-Proust, V.Sazdovitch, A.Matos, J.P.Brandel, J.J.Hauw, S.Haïk, INSERM Avenir team "Human prion diseases", Neuropathology, Salpetriere Hospital, Paris, France; C.A.Maurage, INSERM U422, Anatomy-Pathological Cytology, R. Salengro Hospital, Lille, France; J.L.Laplance, Biochemistry-Molecular Biology, Lariboisiere Hospital, Paris, France
SP englisch
PO Deutschland