Dataset Information

Discrimination of Classical and Atypical BSE by a Distinct Immunohistochemical PrP^Sc Profile.

ABSTRACT: Bovine spongiform encephalopathy (BSE) belongs to the group of transmissible spongiform encephalopathies and is associated with the accumulation of a pathological isoform of the host-encoded glycoprotein, designated prion protein (PrP^Sc). Classical BSE (C-type) and two atypical BSE forms (L- and H-type) are known, and can be discriminated by biochemical characteristics. The goal of our study was to identify type-specific PrP^Sc profiles by using Immunohistochemistry. In our study, brain samples from 21 cattle, intracerebrally inoculated with C-, H-, and L-type BSE, were used. In addition, the corresponding samples from three orally C-type BSE infected animals were also included. From all animals, a lesion and PrP^Sc-profiles of six brain regions were determined. The lesion profile and the neuroanatomical distribution of PrP^Sc was highly consistent between the groups, but the immunohistochemical analysis revealed a distinct PrP^Sc profile for the different BSE-types, which included both the topographic and cellular pattern of PrP^Sc. This qualitative and quantitative analysis of PrP^Sc affected structures sheds new light into the pathogenesis of the different BSE types. Furthermore, immunohistochemical characterization is supported as an additional diagnostic tool in BSE surveillance programs, especially when only formalin-fixed tissue samples are available.

SUBMITTER: Fast C

PROVIDER: S-EPMC9965285 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Discrimination of Classical and Atypical BSE by a Distinct Immunohistochemical PrPSc Profile.

Fast Christine C Graham Catherine C Kaatz Martin M Santiago-Mateo Kristina K Kaatz Tammy T MacPherson Kendra K Balkema-Buschmann Anne A Ziegler Ute U Groschup Martin H MH Czub Stefanie S

Pathogens (Basel, Switzerland) 20230220 2

Bovine spongiform encephalopathy (BSE) belongs to the group of transmissible spongiform encephalopathies and is associated with the accumulation of a pathological isoform of the host-encoded glycoprotein, designated prion protein (PrPSc). Classical BSE (C-type) and two atypical BSE forms (L- and H-type) are known, and can be discriminated by biochemical characteristics. The goal of our study was to identify type-specific PrPSc profiles by using Immunohistochemistry. In our ...[more]

PMID: 36839625

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Project description:Prion diseases are fatal neurodegenerative diseases in mammals with the unique characteristics of misfolding and aggregation of the cellular prion protein (PrPC) to the scrapie prion (PrPSc). Although neuroinflammation and neuronal loss feature within the disease process, the details of PrPC/PrPSc molecular transition to generate different aggregated species, and the correlation between each species and sequence of cellular events in disease pathogenesis are not fully understood. In this study, using mice inoculated with the RML isolate of mouse-adapted scrapie as a model, we applied asymmetric flow field-flow fractionation to monitor PrPC and PrPSc particle sizes and we also measured seeding activity and resistance to proteases. For cellular analysis in brain tissue, we measured inflammatory markers and synaptic damage, and used the isotropic fractionator to measure neuronal loss; these techniques were applied at different timepoints in a cross-sectional study of disease progression. Our analyses align with previous reports defining significant decreases in PrPC levels at pre-clinical stages of the disease and demonstrate that these decreases become significant before neuronal loss. We also identified the earliest PrPSc assemblies at a timepoint equivalent to 40% elapsed time for the disease incubation period; we propose that these assemblies, mostly composed of proteinase K (PK)-sensitive species, play an important role in triggering disease pathogenesis. Lastly, we show that the PK-resistant assemblies of PrPSc that appear at timepoints close to the terminal stage have similar biophysical characteristics, and hence that preparative use of PK-digestion selects for this specific subpopulation. In sum, our data argue that qualitative, as well as quantitative, changes in PrP conformers occur at the midpoint of subclinical phase; these changes affect quaternary structure and may occur at the threshold where adaptive responses become inadequate to deal with pathogenic processes.

Dataset Information

Discrimination of Classical and Atypical BSE by a Distinct Immunohistochemical PrP^Sc Profile.

Publications

Discrimination of Classical and Atypical BSE by a Distinct Immunohistochemical PrP<sup>Sc</sup> Profile.

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