S100a9 Knockdown Decreases the Memory Impairment and the Neuropathology in Tg2576 Mice, AD Animal Model 英文参考文献.docVIP

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S100a9 Knockdown Decreases the Memory Impairment and the Neuropathology in Tg2576 Mice, AD Animal Model 英文参考文献.doc

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S100a9 Knockdown Decreases the Memory Impairment and the Neuropathology in Tg2576 Mice, AD Animal Model 英文参考文献

S100a9KnockdownDecreasestheMemoryImpairment andtheNeuropathologyinTg2576Mice,ADAnimal Model Tae-YoungHa1.,Keun-AChang1.,JeongaKim1,Hye-SunKim1,SeonghanKim1,YoungHaeChong2, Yoo-HunSuh1* 1DepartmentofPharmacology,CollegeofMedicine,NationalCreativeResearchInitiativeCenterforAlzheimer’sDementiaandNeuroscienceResearchInstitute,MRC, SeoulNationalUniversity,Seoul,SouthKorea,2DepartmentofMicrobiology,SchoolofMedicine,EwhaWomansUniversity,Yangcheonku,Seoul,SouthKorea Abstract Inflammation, insoluble protein deposition and neuronal cell loss are important features in the Alzheimer’s disease (AD) brain.ToinvestigatetheregulatorygenesresponsiblefortheneuropathologyinAD,weperformedmicroarrayanalysiswith APPV717I-CT100transgenicmice,ananimalmodelofAD,andisolatedtheS100a9gene,whichencodesaninflammation- associatedcalciumbindingprotein.InanotherADanimalmodel,Tg2576mousebrain,andinhumanADbrain,inductionof S100a9 was confirmed. The endogenous expression of S100a9 was induced by treatment with Ab or CT peptides in a microgliacellline,BV2cells.Inthesecells,silencingstudyofS100a9showedthattheinductionofS100a9increasedthe intracellularcalciumlevelandup-regulatedtheinflammatorycytokines(IL-1bandTNFa)andiNOS.S100a9lentiviralshort hairpin RNA (sh-S100a9) was injected into the hippocampus region of the brains of 13-month-old Tg2576 mice. At two monthsafterinjection,wefoundthatknockdownofS100a9expressionhadimprovedthecognitiondeclineofTg2576mice inthewatermazetask,andhadreducedamyloidplaqueburden.TheseresultssuggestthatS100a9inducedbyAborCT contributestocauseinflammation,whichthenaffectstheneuropathologyincludingamyloidplaquesburdenandimpairs cognitivefunction.Thus,theinhibitionofS100a9isapossibletargetforADtherapy. Citation:HaT-Y,ChangK-A,KimJ,KimH-S,KimS,etal.(2010)S100a9KnockdownDecreasestheMemoryImpairmentandtheNeuropathologyinTg2576Mice, ADAnimalModel.PLoSONE5(1):e8840.doi:10.1371/journal.pone.0008840 Editor:ThierryAme′de′e,UMRCNRS5226-Universite′ Bordeaux2,France ReceivedOctober14