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 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.
Sbriccoli
Marco
M
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. marco.sbriccoli@iss.it
Cardone
Franco
F
Valanzano
Angelina
A
Lu
Mei
M
Graziano
Silvia
S
De Pascalis
Angela
A
Ingrosso
Loredana
L
Zanusso
Gianluigi
G
Monaco
Salvatore
S
Bentivoglio
Marina
M
Pocchiari
Maurizio
M
D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D006224:Cricetinae; D007150:Immunohistochemistry; D008221:Lymphoid Tissue / Q000737:chemistry / Q000473:pathology; D008647:Mesocricetus; D009296:Nasal Cavity / Q000737:chemistry; D009474:Neurons / Q000737:chemistry; D018620:PrPSc Proteins / Q000008:administration & dosage / Q000032:analysis / Q000472:pathogenicity*; D012608:Scrapie / Q000378:metabolism* / Q000473:pathology*
D018620:PrPSc Proteins