Role of Microglia in Neuronal Cell Death in Prion Disease

Brain Pathology - Tập 8 Số 3 - Trang 449-457 - 1998
Armin Giese1, David R. Brown1, Martin H. Groschup2, Claudia Feldmann1, Ingrid Haist2, Hans A. Kretzschmar1
1Institute of Neuropathology, University of Göttingen, Göttingen, Germany
2Federal Research Centre for Virus Diseases of Animals, Tubingen, Germany

Tóm tắt

To elucidate the role played by the prion protein in scrapie pathogenesis, we performed experiments with PrP27–30 isolated from scrapie‐infected hamster brains in cell culture and studied in vivo the temporal and spatial correlation between deposition of the disease‐associated isoform of the prion protein (PrPSc), microglial activation and neuronal cell death in mice infected with scrapie strains 79A, ME7 and RML. The results presented here show that cellular expression of PrPc and the presence of microglia are necessary for the neurotoxicity of PrPScin 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 period of all models studied. Both the time course and the spatial distribution of microglial activation closely resembled the pattern of PrPSc deposition. Microglial activation clearly preceded the detection of apoptotic neuronal cell death which was assessed using the in situ end‐labeling technique (ISEL). Taken together, our results indicate that microglial activation is involved in the neurotoxicity of PrPSc both in vitro and in vivo.

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Brain Pathology

Tập 8 Số 3

449-457

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