Open AccessRole of Microglia in Neuronal Cell Death in Prion Disease
Author(s) -
Giese Armin,
Brown David R.,
Groschup Martin H.,
Feldmann Claudia,
Haist Ingrid,
Kretzschmar Hans A.
Publication year - 1998
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.1998.tb00167.x
Subject(s) - scrapie , microglia , neurotoxicity , in vivo , programmed cell death , biology , incubation period , microbiology and biotechnology , in vitro , gene isoform , apoptosis , hamster , cell , incubation , prion protein , chemistry , immunology , pathology , disease , biochemistry , inflammation , gene , medicine , genetics , toxicity , organic chemistry
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 (PrP Sc ), 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 PrP c and the presence of microglia are necessary for the neurotoxicity of PrP Sc 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 period of all models studied. Both the time course and the spatial distribution of microglial activation closely resembled the pattern of PrP Sc 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 PrP Sc both in vitro and in vivo.