Role of microglia in neuronal cell death in prion disease
Open accessAbstract
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 Scin 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.
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“Moreover, microglia are directly activated by PrPSc in vitro [33,59]; however, such causalities are difficult to prove in vivo.”
Background
- Authors
- Giese, A., Brown, D. R., Groschup, M. H., Feldmann, C., Haist, I., & Kretzschmar, H. A.
- Affiliations
- University of Göttingen (DE)
- Corresponding author
- Kretzschmar, Hans A.
- Venue
- Brain Pathology
- Publisher
- Wiley
- Published
- 1998-07
- Volume
- 8
- Issue
- 3
- Pages
- 449-457
- ISSN
- 1015-6305 (ISSN-L)
- 1750-3639
- PMC
- PMC8098568
- OpenAlex
- W2001312162
- Cited by
- 239
- References
- 28
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 8 · 2017: 8 · 2016: 4 · 2015: 5 · 2014: 6 · 2013: 5 · 2012: 11
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- OpenAgrar (submittedVersion)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- prion disease, scrapie, microglial activation, neuronal cell death, apoptosis, prion protein isoforms, neurotoxicity, scrapie strains, hamster model, mouse model, in situ end-labeling
- MeSH terms
- Animals, Animals, Newborn, Cells, Cultured, Cerebellum, Dose-Response Relationship, Drug, Female, Cricetinae, Immunoenzyme Techniques, Leucine, Mice, Inbred C57BL, Mice, Inbred Strains, Neurons, Scrapie, Time Factors, Apoptosis, Microglia, Mice, Knockout, PrPSc Proteins, PrPC Proteins, Mice
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