Abstract
Bovine spongiform encephalopathy (BSE) has become a public health issue because a recently evolved BSE agent has infected people, yielding an unusual form of Creutzfeld-Jakob disease (CJD). A new CJD agent that provokes similar amyloid plaques and cerebellar pathology was serially propagated. First-passage rats showed obvious clinical signs and activated microglia but had negligible PrP-res (the more protease-resistant form of host PrP) or cerebellar lesions. Microglia and astrocytes may participate in strain selection because the agent evolved, stabilized, and reproducibly provoked BSE-like disease in subsequent passages. Early vacuolar change involving activated microglia and astrocytes preceded significant PrP-res accumulation by more than 50 days. These studies reveal several inflammatory host reactions to an exogenous agent.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amyloid beta-Protein Precursor / analysis
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Animals
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Astrocytes / chemistry
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Astrocytes / ultrastructure*
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Brain / pathology*
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Brain Chemistry
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Cerebellum / chemistry
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Cerebellum / pathology
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Clusterin
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Creutzfeldt-Jakob Syndrome / metabolism
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Creutzfeldt-Jakob Syndrome / pathology*
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Cricetinae
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Cricetulus
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Encephalopathy, Bovine Spongiform / metabolism
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Encephalopathy, Bovine Spongiform / pathology*
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Glial Fibrillary Acidic Protein / genetics
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Glial Fibrillary Acidic Protein / metabolism
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Glycoproteins / analysis
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Inflammation
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Macrophages / chemistry
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Macrophages / ultrastructure
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Mice
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Mice, Inbred Strains
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Microglia / chemistry
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Microglia / ultrastructure*
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Microscopy, Electron
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Molecular Chaperones*
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PrPSc Proteins / analysis*
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PrPSc Proteins / pathogenicity
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RNA / metabolism
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Rats
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Rats, Sprague-Dawley
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Time Factors
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Ubiquitins / analysis
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Vacuoles / ultrastructure
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Virulence
Substances
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Amyloid beta-Protein Precursor
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Clu protein, mouse
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Clusterin
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Glial Fibrillary Acidic Protein
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Glycoproteins
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Molecular Chaperones
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PrPSc Proteins
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Ubiquitins
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RNA