DOI: 10.1111/j.1750-3639.1998.tb00167.x. Role of Microglia in Neuronal Cell Death in Prion Disease

Role of Microglia in Neuronal Cell Death in Prion Disease

10.1111/j.1750-3639.1998.tb00167.x

Crossref journal-article

Wiley

Brain Pathology (311)

Abstract

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.

Bibliography

Giese, A., Brown, D. R., Groschup, M. H., Feldmann, C., Haist, I., & Kretzschmar, H. A. (1998). Role of Microglia in Neuronal Cell Death in Prion Disease. Brain Pathology, 8(3), 449â457. Portico.

Authors 6

Armin Giese (first)
David R. Brown (additional)
Martin H. Groschup (additional)
Claudia Feldmann (additional)
Ingrid Haist (additional)
Hans A. Kretzschmar (additional)

References 28 Referenced 184

10.1099/0022-1317-77-8-1925
10.1038/379339a0
10.1097/00001756-199410270-00017
10.1002/(SICI)1098-1136(199609)18:1<59::AID-GLIA6>3.0.CO;2-Z
10.1038/380345a0
10.1038/356577a0
10.1007/BF03403528
10.1002/j.1460-2075.1996.tb00467.x
10.1038/362543a0
10.1111/j.1750-3639.1995.tb00597.x
10.1523/JNEUROSCI.06-08-02163.1986
10.1007/BF01321071
10.1002/(SICI)1098-1136(199710)21:2<253::AID-GLIA8>3.0.CO;2-7
10.1001/archneur.1996.00550090125018
{'key': 'e_1_2_1_16_2', 'first-page': '1', 'article-title': 'Scrapie prion proteins are synthesized in neurons', 'volume': '122', 'author': 'Kretzschmar HA', 'year': '1986', 'journal-title': 'Am. J. Pathol.'} / Am. J. Pathol. / Scrapie prion proteins are synthesized in neurons by Kretzschmar HA (1986)
10.1016/0304-3940(95)11995-9
10.1242/dev.115.1.117 / Development / The prion protein gene: a role in mouse embryogenesis by Manson J (1992)
10.1093/brain/101.2.333
10.1073/pnas.83.8.2310
10.1016/0896-6273(95)90307-0
10.1016/0922-4106(93)90040-G
10.1073/pnas.90.23.10962
10.1126/science.6801762
10.1001/archneur.1993.00540110011002
10.1073/pnas.89.16.7620
10.1016/0014-5793(96)00610-2
10.1006/exnr.1997.6424
10.1111/j.1365-2990.1994.tb00956.x

Dates

Type	When
Created	15 years, 1 month ago (July 27, 2010, 9:30 a.m.)
Deposited	1 year, 10 months ago (Oct. 28, 2023, 7:39 a.m.)
Indexed	1 week, 2 days ago (Aug. 21, 2025, 12:49 p.m.)
Issued	27 years, 1 month ago (July 1, 1998)
Published	27 years, 1 month ago (July 1, 1998)
Published Online	19 years, 4 months ago (April 5, 2006)
Published Print	27 years, 1 month ago (July 1, 1998)

Funders 0

None

BibTeX

@article{Giese_1998, title={Role of Microglia in Neuronal Cell Death in Prion Disease}, volume={8}, ISSN={1750-3639}, url={http://dx.doi.org/10.1111/j.1750-3639.1998.tb00167.x}, DOI={10.1111/j.1750-3639.1998.tb00167.x}, number={3}, journal={Brain Pathology}, publisher={Wiley}, author={Giese, Armin and Brown, David R. and Groschup, Martin H. and Feldmann, Claudia and Haist, Ingrid and Kretzschmar, Hans A.}, year={1998}, month=jul, pages={449–457} }

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