NR AGRY
AU Kordek,R.; Hainfellner,J.A.; Liberski,P.P.; Budka,H.
TI Deposition of the prion protein (PrP) during the evolution of experimental Creutzfeldt-Jakob disease
QU Acta Neuropathologica 1999 Dec; 98(6): 597-602
PT journal article
AB We studied the immunocytochemical distribution of the prion or proteinase-resistant protein (PrP) during the evolution of experimental Creutzfeldt-Jakob disease (CJD) in mice. Fifty-one brains were collected up to 22 weeks following intracerebral inoculation with the Fujisaki strain of the CJD agent. Slides were also immunostained for apolipoprotein E (apoE) and glial fibrillary acidic protein. Vacuolar changes with focal astrocytosis first occurred around the needle track at week 2 and later spread along white matter tracks. Until week 12, changes were asymmetrical, affecting more the side of inoculation. Spongiform change and astrogliosis spread subsequently to the gray matter. Time course and intensity of spongiform change and immunocytochemistry for PrP were discrepant: in most brain regions, severe vacuolation preceded immunocytochemically detectable PrP accumulation. PrP deposits in form of small dots were first detectable at week 6 in the area surrounding the needle track. After week 7, plaque-like amorphous PrP deposits were observed in white matter pathways. Finally, PrP was detectable also in basal ganglia and in the dorsal hippocampus (week 13) and in the neocortex (week 17), as the synaptic type of PrP immunopositivity. In the hippocampus, diffuse PrP deposits paralleled spongiform change, while in the cortex severe vacuolation was accompanied only by weak synaptic PrP deposits. Immunocytochemically detectable apoE was restricted to compact plaque-type PrP deposits after week 15. We conclude that disease-specific neuropathology spreads from the needle track along white matter pathways towards the gray matter; in this model, there is some discrepancy between development of tissue pathology and immunocytochemically detectable deposition of PrP. Immunocytochemically detectable apoE deposition follows PrP accumulation.
ZR 37 Zitate
IN Mäuse wurden mit dem an Mäuse adaptierten Fujisaki-Creutzfeldt-Jakob-Stamm (wahrscheinlich von einem Gerstmann-Sträussler-Scheinker-Patienten) intrazerebral infiziert. Wöchentlich wurden zwei Mäuse getötet, um die Entwicklung der Schädigung sowie der Ablagerung von proteaseresistentem Prionprotein zu verfolgen. Die ersten Vakuolen wurden 2 Wochen nach der Inokulation an den Einstichstellen erkennbar und breiteten sich danach entlang der Nervenbahnen aus. Bis zur 12. Woche waren die Gehirnhälften mit den Einstichstellen stärker betroffen. Später griffen die Vakuolisierung und die typische Astrogliose auch auf die graue Hirnsubstanz über. In den meisten Hirnregionen waren bereits starke spongiforme Veränderungen beobachtbar, bevor das proteaseresistente Prionprotein nachgewiesen werden konnte. Um die Einstichstelle war dies erst nach 6 Wochen der Fall. Nach 7 Wochen wurden amorphe Prionproteinplaques entlang der weißen Nervenbahnen markiert. Ab der 13. Woche waren die Prionamyloide auch in den Basalganglien und dem Hippocampus, ab der 17. Woche schließlich auch im Neocortex erkennbar. Im Hippocampus traten diffuse Prionproteinablagerungen gleichzeitig mit den ersten Vakuolen auf.
MH Animal; Apolipoproteins E/analysis; Brain/pathology; Creutzfeldt-Jakob Syndrome/*pathology; Disease Models, Animal; Human; Male; Mice; Middle Age; Prions/*analysis; Support, Non-U.S. Gov't
AD
Radzislaw Kordek (1)(2)(3), Johannes A. Hainfellner (1), Pawel P. Liberski (1)(2)(3), H. Budka (1);
(1) Institute of Neurology, University of Vienna, AKH 04J, A-1097 Wien, Austria e-mail: h.budka@akh-wien.ac.at, Tel.: +43-1-40400-5501, Fax: +43-1-40400-5511
(2) Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
(3) Department of Molecular Biology, Chair of Oncology, Medical Academy Lodz, Lodz, Poland
SP englisch
PO Deutschland
OR Prion-Krankheiten 5