NR AHBI
AU Lasmezas,C.I.; Deslys,J.P.; Demaimay,R.; Adjou,K.T.; Hauw,J.J.; Dormont,D.
TI Strain specific and common pathogenic events in murine models of scrapie and bovine spongiform encephalopathy
QU Journal of General Virology 1996 Jul; 77(7): 1601-9
PT journal article
AB The development of transmissible spongiform encephalopathies in experimental models depends on two major factors: the intracerebral accumulation of an abnormal, protease-resistant isoform of PrP (PrPres), which is a host protein mainly expressed in neurons; and the existence of different strains of agent. In order to make a distinction between pathogenic mechanisms depending upon the accumulation of host-derived PrPres and the strain-specific effects, we quantified and compared the sequence of molecular [PrPres and glial fibrillary acidic protein (GFAP) accumulation] and pathological events in the brains of syngeneic mice throughout the course of infection with two different strains of agent. The bovine spongiform encephalopathy (BSE) agent exhibits properties different from any known scrapie source and has been studied in comparison with a classical scrapie strain. Convergent kinetic data in both models confirmed the cause-effect relationship between PrPres and pathological changes and showed that PrPres accumulation is directly responsible for astrocyte activation in vivo. Moreover, we observed a threshold level of PrPres for this effect on astroglial cells. However, despite similar infectivity titres, the BSE model produced less PrPres than scrapie, and the relative importance of gliosis was higher. The comparison of the molecular and pathological features after intracerebral or intraperitoneal inoculation also revealed differences between the models. Therefore, the mechanisms leading to the targeting and the fine regulation of the molecular events seem to be independent of the host PrP and to depend upon the agent. The possible involvement of a regulatory molecule accounting for these specificities has to be considered.
IN Die Autoren glauben gezeigt zu haben, dass die Akkumulation des proteaseresistenten Prionproteins in Mäusen direkt verantwortlich für die Aktivierung der Astrozyten sei und das es eine Schwellenkonzentration proteaseresistenter Prionproteine für diesen Effekt auf die Astrogliazellen gebe. Trotz angeblich ähnlichen Infektionstitern produzierten BSE-infizierte Mäuse weniger proteaseresistentes Prionprotein als die mit Scrapie infizierten Mäuse. Trotzdem soll die Gliose bei den BSE-Mäusen eine größere Rolle spielen. Auch bei anderen molekularen und pathologischen Aspekten gab es Unterschiede in Abhängigkeit vom verwendeten Erreger. Dummerweise ziehen die Autoren aus diesen altbekannten Selbstverständlichkeiten den Schluß, der Krankheitsverlauf sei unabhängig vom Wirtsprionprotein.
ZR 48
MH Animal; Astrocytes/metabolism; Cattle; Disease Models, Animal; Encephalopathy, Bovine Spongiform/*etiology/pathology/physiopathology; Glial Fibrillary Acidic Protein/metabolism; Mice; Mice, Inbred C57BL; PrPsc Proteins/*pathogenicity; Scrapie/*etiology/pathology/physiopathology; Sheep; Support, Non-U.S. Gov't; Time Factors
AD Service de Neurovirologie, DSV/DRM/CRSSA, Commissariat a L'Energie Atomique, Fontenay-aux-Roses, France.
SP englisch
PO England
OR Prion-Krankheiten L