STRAIN-SPECIFIC AND COMMON PATHOGENIC EVENTS IN MURINE MODELS OF SCRAPIE AND BOVINE SPONGIFORM ENCEPHALOPATHY

The development of transmissible spongiform encephalopathies in experi mental models depends on two major factors: the intracerebral accumula tion of an abnormal, protease-resistant isoform of PrP (PrPres), which is a host protein mainly expressed in neurons; and the existence of d ifferent strains of agent, In order to make a distinction between path ogenic mechanisms depending upon the accumulation of host-derived PrPr es and the strain-specific effects, we quantified and compared the seq uence 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 compa rison with a classical scrapie strain, Convergent kinetic data in both models confirmed the cause-effect relationship between PrPres and pat hological changes and showed that PrPres accumulation is directly resp onsible for astrocyte activation in vivo. Moreover, we observed a thre shold level of PrPres for this effect on astroglial cells, However, de spite similar infectivity titres, the BSE model produced less PrPres t han scrapie, and the relative importance of gliosis was higher, The co mparison of the molecular and pathological features after intracerebra l or intraperitoneal inoculation also revealed differences between the models, Therefore, the mechanisms leading to the targeting and the fi ne regulation of the molecular events seem to be independent of the ho st PrP and to depend upon the agent, The possible involvement of a reg ulatory molecule accounting for these specificities has to be consider ed.