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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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Published in: | Acta neuropathologica 2009-02, Vol.117 (2), p.175-184 |
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creator | Sbriccoli, Marco Cardone, Franco Valanzano, Angelina Lu, Mei Graziano, Silvia De Pascalis, Angela Ingrosso, Loredana Zanusso, Gianluigi Monaco, Salvatore Bentivoglio, Marina Pocchiari, Maurizio |
description | 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. |
doi_str_mv | 10.1007/s00401-008-0474-z |
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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.</description><identifier>ISSN: 0001-6322</identifier><identifier>EISSN: 1432-0533</identifier><identifier>DOI: 10.1007/s00401-008-0474-z</identifier><identifier>PMID: 19107494</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>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</subject><ispartof>Acta neuropathologica, 2009-02, Vol.117 (2), p.175-184</ispartof><rights>Springer-Verlag 2008</rights><rights>Springer-Verlag 2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-2ddf29607797a9574472c018508073765509f9a3c30deadd57e6964ad12e3293</citedby><cites>FETCH-LOGICAL-c400t-2ddf29607797a9574472c018508073765509f9a3c30deadd57e6964ad12e3293</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19107494$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sbriccoli, Marco</creatorcontrib><creatorcontrib>Cardone, Franco</creatorcontrib><creatorcontrib>Valanzano, Angelina</creatorcontrib><creatorcontrib>Lu, Mei</creatorcontrib><creatorcontrib>Graziano, Silvia</creatorcontrib><creatorcontrib>De Pascalis, Angela</creatorcontrib><creatorcontrib>Ingrosso, Loredana</creatorcontrib><creatorcontrib>Zanusso, Gianluigi</creatorcontrib><creatorcontrib>Monaco, Salvatore</creatorcontrib><creatorcontrib>Bentivoglio, Marina</creatorcontrib><creatorcontrib>Pocchiari, Maurizio</creatorcontrib><title>Neuroinvasion of the 263K scrapie strain after intranasal administration occurs through olfactory-unrelated pathways</title><title>Acta neuropathologica</title><addtitle>Acta Neuropathol</addtitle><addtitle>Acta Neuropathol</addtitle><description>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. 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Academic</collection><jtitle>Acta neuropathologica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sbriccoli, Marco</au><au>Cardone, Franco</au><au>Valanzano, Angelina</au><au>Lu, Mei</au><au>Graziano, Silvia</au><au>De Pascalis, Angela</au><au>Ingrosso, Loredana</au><au>Zanusso, Gianluigi</au><au>Monaco, Salvatore</au><au>Bentivoglio, Marina</au><au>Pocchiari, Maurizio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroinvasion of the 263K scrapie strain after intranasal administration occurs through olfactory-unrelated pathways</atitle><jtitle>Acta neuropathologica</jtitle><stitle>Acta Neuropathol</stitle><addtitle>Acta Neuropathol</addtitle><date>2009-02-01</date><risdate>2009</risdate><volume>117</volume><issue>2</issue><spage>175</spage><epage>184</epage><pages>175-184</pages><issn>0001-6322</issn><eissn>1432-0533</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>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.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>19107494</pmid><doi>10.1007/s00401-008-0474-z</doi><tpages>10</tpages></addata></record> |
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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 |
title | Neuroinvasion of the 263K scrapie strain after intranasal administration occurs through olfactory-unrelated pathways |
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