Neuroinvasion of the 263K scrapie strain after intranasal administration occurs through olfactory-unrelated pathways

The olfactory system has been implicated in the pathogenesis of transmissible spongiform encephalopathies (TSEs). To examine this issue and identify the pattern of TSE agent spread after intranasal administration, we inoculated a high-infectious dose of neurotropic scrapie strain 263K into the nasal...

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Bibliographic Details
Published in:Acta neuropathologica 2009-02, Vol.117 (2), p.175-184
Main Authors: Sbriccoli, Marco, Cardone, Franco, Valanzano, Angelina, Lu, Mei, Graziano, Silvia, De Pascalis, Angela, Ingrosso, Loredana, Zanusso, Gianluigi, Monaco, Salvatore, Bentivoglio, Marina, Pocchiari, Maurizio
Format: Article
Language:English
Subjects:
Administration, Intranasal
Animals
Brain
Brain - pathology
Brain Chemistry
Creutzfeldt-Jakob disease
Cricetinae
Immunohistochemistry
Infections
Lymphoid Tissue - chemistry
Lymphoid Tissue - pathology
Medicine
Medicine & Public Health
Mesocricetus
Nasal Cavity - chemistry
Neurons - chemistry
Neurosciences
Original Paper
Pathogenesis
Pathology
PrPSc Proteins - administration & dosage
PrPSc Proteins - analysis
PrPSc Proteins - pathogenicity
Scrapie - metabolism
Scrapie - pathology
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Summary:The olfactory system has been implicated in the pathogenesis of transmissible spongiform encephalopathies (TSEs). To examine this issue and identify the pattern of TSE agent spread after intranasal administration, we inoculated a high-infectious dose of neurotropic scrapie strain 263K into the nasal cavity of Syrian hamsters. All animals allowed to survive became symptomatic with a mean incubation period of 162.4 days. Analysis at different time points revealed deposition of the pathological prion protein (PrP TSE ) in nasal-associated lymphoid tissues in the absence of brain involvement from 80 days post-infection (50% of the incubation period). Olfactory-related structures and brainstem nuclei were involved from 100 days post-inoculation (62% of the incubation period) when animals were still asymptomatic. Intriguingly, vagal or trigeminal nuclei were identified as early sites of PrP TSE deposition in some pre-symptomatic animals. These findings indicate that the 263K scrapie agent is unable to effectively spread from the olfactory neuroepithelium to the olfactory-related structures and that, after intranasal inoculation, neuroinvasion occurs through olfactory-unrelated pathways.
ISSN:0001-6322
1432-0533
DOI:10.1007/s00401-008-0474-z