ROLE OF MICROGLIA IN NEURONAL CELL-DEATH IN PRION DISEASE

To elucidate the role played by the prion protein in scrapie pathogene sis, we performed experiments with PrP27-30 isolated from scrapie-infe cted hamster brains in cell culture and studied in vivo the temporal a nd spatial correlation between deposition of the disease-associated is oform of the prion protein (PrPSc), microglial activation and neuronal cell death in mice infected with scrapie strains 79A, ME7 and RML. Th e results presented here show that cellular expression of PrPc and the presence of microglia are necessary for the neurotoxicity of PrPSc in vitro, in vivo, accumulation of protease-resistant prion protein was detected early in the incubation period using the histoblot technique. Microglial activation was also detected early in the incubation perio d of all models studied. Both the time course and the spatial distribu tion of microglial activation closely resembled the pattern of PrPSc d eposition. Microglial activation clearly preceded the detection of apo ptotic neuronal cell death which was assessed using the in situ end-la beling technique (ISEL). Taken together, our results indicate that mic roglial activation is involved in the neurotoxicity of PrPSc both in v itro and in vivo.