PrP Expression, PrPSc Accumulation and Innervation of Splenic Compartments in Sheep Experimentally Infected with Scrapie 英文参考文献.docVIP

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PrP Expression, PrPSc Accumulation and Innervation of Splenic Compartments in Sheep Experimentally Infected with Scrapie 英文参考文献.doc

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PrP Expression, PrPSc Accumulation and Innervation of Splenic Compartments in Sheep Experimentally Infected with Scrapie 英文参考文献

PrPExpression,PrPSc AccumulationandInnervationof SplenicCompartmentsinSheepExperimentallyInfected withScrapie RandiS?rby1*,LarsAustb?1,CharlesMcL.Press1,GretheSkretting2,ThorLandsverk1,ArildEspenes1 1DepartmentofBasicSciencesandAquaticMedicine,NorwegianSchoolofVeterinaryScience,Oslo,Norway,2HaematologicalResearchLaboratory,Ulleva?lUniversity Hospital,Oslo,Norway Abstract Background: In prion disease, the peripheral expression of PrPC is necessary for the transfer of infectivity to the central nervoussystem.Thespleenisinvolvedinneuroinvasionandneuraldisseminationinpriondiseasesbutthenatureofthis involvementisnotknown.ThepresentstudyundertooktheinvestigationofthespatialrelationshipbetweensitesofPrPSc accumulation, localisation of nerve fibres and PrPC expression in the tissue compartments of the spleen of scrapie- inoculatedandcontrolsheep. Methodology/PrincipalFindings:LasermicrodissectionandquantitativePCRwereusedtodeterminePrPmRNAlevelsand resultswerecomparedwithimmunohistochemicalprotocolstodistinguishPrPCandPrPScintissuecompartmentsofthe spleen.Insheepexperimentallyinfectedwithscrapie,themajorsitesofaccumulationofPrPSc inthespleen,namelythe lymphoidnodulesandthemarginalzone,expressedlowlevelsofPrPmRNA.Doubleimmunohistochemicallabellingfor PrPScandthepan-nervefibremarker,PGP,wasusedtoevaluatethedensityofinnervationofsplenictissuecompartments andtheintimacyofassociationbetweenPrPScandnerves.Somenervefibreswereobservedtoaccompanybloodvessels intothePrPSc-ladengerminalcentres.However,thecloseassociationbetweennervesandPrPScwasmostapparentinthe marginalzone.OthersitesofcloseassociationwereadjacenttothewallofthecentralarteryofPALSandtheouterrimof germinalcentres. Conclusions/Significance:ThefindingssuggestthatthedegreeofPrPScaccumulationdoesnotdependontheexpression levelofPrPC.Thoughseveralspleniccompartmentsmaycontributetoneuroinvasion,themarginalzonemayplayacentral roleinbeingthecompartmentwithmostapparentassociationbetweennervesandPrPSc. Citation:S?rbyR,Au