ArticlePLoS pathogens2012
Prion pathogenesis is faithfully reproduced in cerebellar organotypic slice cultures.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 79 citations in OpenAlex.
- Time-dependent transcriptomic response to scrapie exposure in ovine MSC-derived neuron-like cells.Frontiers in cellular and infection microbiology · 2026Article
- Prions and protein aggregates as pathogens, self-propagating structures, biomarkers, and therapeutic targets.Microbiology and molecular biology reviews : MMBR · 2025Review
- Prion replication in organotypic brain slice cultures is distinct from in vivo inoculation and is species dependent.Acta neuropathologica communications · 2025Article
- Distinct patterns of prion strain deposition and toxicity in a novel whole brain organotypic slice culture system.Scientific reports · 2025Article
- Review
- Salivary Organotypic Tissue Culture: An Ex-vivo 3D Model for Studying Radiation-Induced Injury of Human Salivary Glands.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Article
- Genetically engineered cellular models of prion propagation.Cell and tissue research · 2023Review
- Mechanisms of prion-induced toxicity.Cell and tissue research · 2023Review
- Antibody binding modulates the dynamics of the membrane-bound prion protein.Biophysical journal · 2022Article
- A high-content neuron imaging assay demonstrates inhibition of prion disease-associated neurotoxicity by an anti-prion protein antibody.Scientific reports · 2022Article
- Brain aging is faithfully modelled in organotypic brain slices and accelerated by prions.Communications biology · 2022Article
- Review
- Ligands binding to the prion protein induce its proteolytic release with therapeutic potential in neurodegenerative proteinopathies.Science advances · 2021Article
- Loss of PIKfyve drives the spongiform degeneration in prion diseases.EMBO molecular medicine · 2021Article
- From Cell Culture to Organoids-Model Systems for Investigating Prion Strain Characteristics.Biomolecules · 2021Review
- Protective anti-prion antibodies in human immunoglobulin repertoires.EMBO molecular medicine · 2020Article
- POSCAbilities: The Application of the Prion Organotypic Slice Culture Assay to Neurodegenerative Disease Research.Biomolecules · 2020Review
- An Ex Vivo Brain Slice Culture Model of Chronic Wasting Disease: Implications for Disease Pathogenesis and Therapeutic Development.Scientific reports · 2020Article
- Differential Membrane Binding and Seeding of Distinct α-Synuclein Fibrillar Polymorphs.Biophysical journal · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prions cause neurodegeneration in vivo, yet prion-infected cultured cells do not show cytotoxicity. This has hampered mechanistic studies of prion-induced neurodegeneration. Here we report that prion-infected cultured organotypic cerebellar slices (COCS) experienced progressive spongiform neurodegeneration closely reproducing prion disease, with three different prion strains giving rise to three distinct patterns of prion protein deposition. Neurodegeneration did not occur when PrP was genetically removed from neurons, and a comprehensive pharmacological screen indicated that neurodegeneration was abrogated by compounds known to antagonize prion replication. Prion infection of COCS and mice led to enhanced fodrin cleavage, suggesting the involvement of calpains or caspases in pathogenesis. Accordingly, neurotoxicity and fodrin cleavage were prevented by calpain inhibitors but not by caspase inhibitors, whereas prion replication proceeded unimpeded. Hence calpain inhibition can uncouple prion replication from its neurotoxic sequelae. These data validate COCS as a powerful model system that faithfully reproduces most morphological hallmarks of prion infections. The exquisite accessibility of COCS to pharmacological manipulations was instrumental in recognizing the role of calpains in neurotoxicity, and significantly extends the collection of tools necessary for rigorously dissecting prion pathogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.