NDLI: Prions can infect primary cultured neurons and astrocytes and promote neuronal cell death

Content Provider	PubMed Central
Author	Sabrina, Cronier Laude, Hubert Peyrin, Jean-michel
Copyright Year	2004
Abstract	Transmissible spongiform encephalopathies arise as a consequence of infection of the central nervous system by prions, where neurons and glial cells are regarded as primary targets. Neuronal loss and gliosis, associated with the accumulation of misfolded prion protein (PrP), are hallmarks of prion diseases; yet the mechanisms underlying such disorders remain unclear. Here we introduced a cell system based on primary cerebellar cultures established from transgenic mice expressing ovine PrP and then exposed to sheep scrapie agent. Upon exposure to low doses of infectious agent, such cultures, unlike cultures originating from PrP null mice, were found to accumulate de novo abnormal PrP and infectivity, as assessed by mouse bioassay. Importantly, using astrocyte and neuron/astrocyte cocultures, both cell types were found capable of sustaining efficient prion propagation independently, leading to the production of proteinase K-resistant PrP of the same electrophoretic profile as in diseased brain. Moreover, contrasting with data obtained in chronically infected cell lines, late-occurring apoptosis was consistently demonstrated in the infected neuronal cultures. Our results provide evidence that primary cultured neural cells, including postmitotic neurons, are permissive to prion replication, thus establishing an approach to study the mechanisms involved in prion-triggered neurodegeneration at a cellular level.
Related Links	http://dx.doi.org/10.1073/pnas.0402725101
Ending Page	12276
Page Count	6
Starting Page	12271
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	33
Volume Number	101
Language	English
Publisher	National Academy of Sciences
Publisher Date	2004-08-17
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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