Beta-Amyloid Downregulates MDR1-P-Glycoprotein (Abcb1) Expression at the Blood-Brain Barrier in Mice英文文献资料.docVIP

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Beta-Amyloid Downregulates MDR1-P-Glycoprotein (Abcb1) Expression at the Blood-Brain Barrier in Mice英文文献资料.doc

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Beta-Amyloid Downregulates MDR1-P-Glycoprotein (Abcb1) Expression at the Blood-Brain Barrier in Mice英文文献资料

SAGE-HindawiAccesstoResearch InternationalJournalofAlzheimer’sDisease Volume2011,ArticleID690121,6pages doi:10.4061/2011/690121 ResearchArticle Beta-AmyloidDownregulatesMDR1-P-Glycoprotein(Abcb1) ExpressionattheBlood-BrainBarrierinMice AnjaBrenn, 1 MarkusGrube, 2 MichelePeters, 1 1 2 AndreaFischer, GabrieleJedlitschky, HeyoK.Kroemer, 2 RolfW.Warzok, 1 andSilkeVogelgesang 1 1 2 DepartmentofNeuropathology,InstituteofPathology,UniversityofGreifswald,17487Greifswald,Germany DepartmentofPharmacology,ResearchCenterofPharmacologyandExperimentalTherapeutics,UniversityofGreifswald, 17487Greifswald,Germany CorrespondenceshouldbeaddressedtoSilkeVogelgesang,silke.vogelgesang@uni-greifswald.de Received26January2011;Accepted4April2011 AcademicEditor:BrianJ.Balin Copyright?2011AnjaBrennetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. NeurovasculardysfunctionisanimportantcomponentofAlzheimer’sdisease,leadingtoreducedclearanceacrosstheblood-brain barrierandaccumulationofneurotoxicβ-amyloid(Aβ)peptidesinthebrain.IthasbeenshownthattheABCtransportproteinP- glycoprotein(P-gp,ABCB1)isinvolvedintheexportofAβfromthebrainintotheblood.TodeterminewhetherAβin?uencesthe expressionofkeyAβtransporters,westudiedthee?ectsof1-daysubcutaneousAβ1-40andAβ1-42administrationviaAlzetmini- osmoticpumpsonP-gp,BCRP,LRP1,andRAGEexpressioninthebrainof90-day-oldmaleFVBmice.Ourresultsdemonstrate signi?cantlyreducedP-gp,LRP1,andRAGEmRNAexpressioninmicetreatedwithAβ1-42comparedtocontrols,whileBCRP expressionwasnota?ected.TheexpressionofthefourproteinswasunchangedinmicetreatedwithAβ1-40orreverse-sequence peptides.These?ndingsindicatethat,inadditiontotheage-relateddecreaseofP-gpexpression,Aβ1-42itselfdownregulatesthe expressionofP-gpandotherAβ-transporters,whichcouldexacerbatetheintracerebralaccumulationofAβandtherebyaccelerate neurodegenerationinAlzhei