5 results on '"Calvo, Patricia"'
Search Results
2. Enhanced neuroinvasion by smaller, soluble prions.
- Author
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Bett, Cyrus, Lawrence, Jessica, Kurt, Timothy D., Orru, Christina, Aguilar-Calvo, Patricia, Kincaid, Anthony E., Surewicz, Witold K., Caughey, Byron, Chengbiao Wu, and Sigurdson, Christina J.
- Subjects
PRION diseases ,NEURODEGENERATION ,AXONAL transport - Abstract
Infectious prion aggregates can propagate from extraneural sites into the brain with remarkable efficiency, likely transported via peripheral nerves. Yet not all prions spread into the brain, and the physical properties of a prion that is capable of transit within neurons remain unclear. We hypothesized that small, diffusible aggregates spread into the CNS via peripheral nerves. Here we used a structurally diverse panel of prion strains to analyze how the prion conformation impacts transit into the brain. Two prion strains form fibrils visible ultrastructurally in the brain in situ, whereas three strains form diffuse, subfibrillar prion deposits and no visible fibrils. The subfibrillar strains had significantly higher levels of soluble prion aggregates than the fibrillar strains. Primary neurons internalized both the subfibrillar and fibril-forming prion strains by macropinocytosis, and both strain types were transported from the axon terminal to the cell body in vitro. However in mice, only the predominantly soluble, subfibrillar prions, and not the fibrillar prions, were efficiently transported from the tongue to the brain. Sonicating a fibrillar prion strain increased the solubility and enabled prions to spread into the brain in mice, as evident by a 40% increase in the attack rate, indicating that an increase in smaller particles enhances prion neuroinvasion. Our data suggest that the small, highly soluble prion particles have a higher capacity for transport via nerves. These findings help explain how prions that predominantly assemble into subfibrillar states can more effectively traverse into and out of the CNS, and suggest that promoting fibril assembly may slow the neuron-to-neuron spread of protein aggregates. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
3. Goat K222-PrPC polymorphic variant does not provide resistance to atypical scrapie in transgenic mice.
- Author
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Aguilar-Calvo, Patricia, Espinosa, Juan-Carlos, Andréoletti, Olivier, González, Lorenzo, Orge, Leonor, Juste, Ramón, and Torres, Juan-María
- Abstract
Host prion (PrP
C ) genotype is a major determinant for the susceptibility to prion diseases. The Q/K222 -PrPC polymorphic variant provides goats and mice with high resistance against classical scrapie and bovine spongiform encephalopathy (BSE); yet its effect against atypical scrapie is unknown. Here, transgenic mice expressing the goat wild-type (wt) or the K222 -PrPC variant were intracerebrally inoculated with several natural cases of atypical scrapie from sheep and goat and their susceptibility to the prion disease was determined. Goat wt and K222 -PrPC transgenic mice were 100% susceptible to all the atypical scrapie isolates, showing similar survival times and almost identical disease phenotypes. The capacity of the K222 -PrPC variant to replicate specifically the atypical scrapie strain as efficiently as the goat wt PrPC , but not the classical scrapie or cattle-BSE as previously reported, further suggests the involvement of concrete areas of the host PrPC in the strain-dependent replication of prions. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
4. Further characterisation of transmissible spongiform encephalopathy phenotypes after inoculation of cattle with two temporally separated sources of sheep scrapie from Great Britain.
- Author
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Konold, Timm, Nonno, Romolo, Spiropoulos, John, Chaplin, Melanie J., Stack, Michael J., Hawkins, Steve A. C., Cawthraw, Saira, Wilesmith, John W., Wells, Gerald A. H., Agrimi, Umberto, Di Bari, Michele A., Andréoletti, Olivier, Espinosa, Juan C., Aguilar-Calvo, Patricia, and Torres, Juan M.
- Subjects
BOVINE spongiform encephalopathy diagnosis ,CATTLE diseases ,RETROSPECTIVE studies ,LABORATORY mice ,WESTERN immunoblotting - Abstract
Background: The infectious agent responsible for the bovine spongiform encephalopathy (BSE) epidemic in Great Britain is a transmissible spongiform encephalopathy (TSE) strain with uniform properties but the origin of this strain remains unknown. Based on the hypothesis that classical BSE may have been caused by a TSE strain present in sheep, cattle were inoculated intracerebrally with two different pools of brains from scrapie-affected sheep sourced prior to and during the BSE epidemic to investigate resulting disease phenotypes and characterise their causal agents by transmission to rodents. Results: As reported in 2006, intracerebral inoculation of cattle with pre-1975 and post-1990 scrapie brain pools produced two distinct disease phenotypes, which were unlike classical BSE. Subsequent to that report none of the remaining cattle, culled at 10 years post inoculation, developed a TSE. Retrospective Western immunoblot examination of the brains from TSE cases inoculated with the pre-1975 scrapie pool revealed a molecular profile similar to L-type BSE. The inoculation of transgenic mice expressing the bovine, ovine, porcine, murine or human prion protein gene and bank voles with brains from scrapie-affected cattle did not detect classical or atypical BSE strains but identified two previously characterised scrapie strains of sheep. Conclusions: Characterisation of the causal agents of disease resulting from exposure of cattle to naturally occurring scrapie agents sourced in Great Britain did not reveal evidence of classical or atypical BSE, but did identify two distinct previously recognised strains of scrapie. Although scrapie was still recognizable upon cattle passage there were irreconcilable discrepancies between the results of biological strain typing approaches and molecular profiling methods, suggesting that the latter may not be appropriate for the identification and differentiation of atypical, particularly L-type, BSE agents from cattle experimentally infected with a potential mixture of classical scrapie strains from sheep sources. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
5. Goat K 222 -PrP C polymorphic variant does not provide resistance to atypical scrapie in transgenic mice.
- Author
-
Aguilar-Calvo P, Espinosa JC, Andréoletti O, González L, Orge L, Juste R, and Torres JM
- Abstract
Host prion (PrP
C ) genotype is a major determinant for the susceptibility to prion diseases. The Q/K222 -PrPC polymorphic variant provides goats and mice with high resistance against classical scrapie and bovine spongiform encephalopathy (BSE); yet its effect against atypical scrapie is unknown. Here, transgenic mice expressing the goat wild-type (wt) or the K222 -PrPC variant were intracerebrally inoculated with several natural cases of atypical scrapie from sheep and goat and their susceptibility to the prion disease was determined. Goat wt and K222 -PrPC transgenic mice were 100% susceptible to all the atypical scrapie isolates, showing similar survival times and almost identical disease phenotypes. The capacity of the K222 -PrPC variant to replicate specifically the atypical scrapie strain as efficiently as the goat wt PrPC , but not the classical scrapie or cattle-BSE as previously reported, further suggests the involvement of concrete areas of the host PrPC in the strain-dependent replication of prions.- Published
- 2016
- Full Text
- View/download PDF
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