theracurmin ameliorates cognitive dysfunctions in 5xfad mice by improving synaptic function and mitigating oxidative stress jihyun kim论文.pdf

该【theracurmin ameliorates cognitive dysfunctions in 5xfad mice by improving synaptic function and mitigating oxidative stress jihyun kim论文 】是由【小舍儿】上传分享，文档一共【9】页，该文档可以免费在线阅读，需要了解更多关于【theracurmin ameliorates cognitive dysfunctions in 5xfad mice by improving synaptic function and mitigating oxidative stress jihyun kim论文 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。OriginalArticleBiomolTher27(3),327-335(2019)TheracurminAmelioratesCognitiveDysfunctionsin5XFADMicebyImprovingSynapticFunctionandMitigatingOxidativeStressJihyunKim1,?,JaehoonKim1,?,ZhouchiHuang3,NayeonGoo1,HoJungBae1,YongwooJeong1,HoJaePark2,MudanCai1,KyungnamCho1,SeoYunJung1,SooKyungBae3andJongHoonRyu1,2,*Departmentsof1LifeandNanopharmaceuticalScience,2OrientalPharmaceuticalScience,KyungHeeUniversity,Seoul02447,3CollegeofPharmacyandIntegratedResearchInstituteofParmaceuticalSciences,TheCatholicUniversityofKorea,Bucheon14662,RepublicofKoreaAbstractAstheelderlypopulationisincreasing,Alzheimer’sdisease(AD),thedevelopmentofnewth-,weexaminedtheeffectsofTheracurminoncognitivedeclineusing5XFADmice,,(100,300and1,000mg/kg)-treatedmiceshowedsignificantameliorationinrecognitionparedthoseofthevehicle-,theantioxidantactivitiesofTheracurminwereinvestigatedbymeasuringthesuperoxidedismutase(SOD)activity,malondialdehyde(MDA)andglutathione(GSH)-,weobservedthatTheracurminadministrationelevatedtheexpressionlevelsofsynap-ponents,includingsynaptophysinandpostsynapticdensityprotein95,anddecreasedtheexpressionlevelsofionizedcalcium-bindingadaptermolecule1(Iba-1),,:Theracurmin,Alzheimer’sdisease,Recognitionmemory,Spatialmemory,Antioxidativeactivity,ponentpetitiveNMDAreceptorantagonists,suchasmemantine,-significantimprovementsinthepharmacotherapyforAD,pa-pectancyofhumanbeingisincreasing,andtherefore,age-tientsexperienceseveraldrug-associatedadverseeffects,eofgreatinterest(Brown,2015;suchasdiarrhea,nauseaorinsomnia(ShintaniandUchida,al.,2017).Dementiaisadegenerativeage-related1997;Hashimotoetal.,2000).Therefore,theeffortstofinddisease,-noveltherapieswithfewadverseeffectsandhighefficacytomentiaeveryyear(Gulland,2012).Alzheimer’sdisease(AD)-PreventiveinterventionsareoptionsforADtherapyand,terizedbythedeficitofcognitivefunctioncausedbytheac-therefore,recentstudieshavefocusedontheantioxidativeorcumulationofamyloidβ(Aβ)-anti-inflammatoryagents(Shadfaretal.,2015;Giubilei,2016;alshavebeenconductedtoattempttoclearAβproteinsfromBakhtiarietal.,2017).Asaresult,manypossibleantioxidantsbraintissues,butunfortunately,eshavenothavebeenexploredandsuggestedaspotentialoptionsforADbeenobtained(KarranandDeStrooper,2016).Intheclinic,.(Zingiberaceae)istherefore,acetylcholinesterase(AChE)inhibitors,includingoneofthemostpopulardietarysupplementsbecauseofitsesshttps:///.046ReceivedMar13,2019RevisedApr3,eptedApr5,2019PublishedOnlineApr19,2019-mercialLicense(/licens-*CorrespondingAuthores/by-nc//)mercialuse,distribution,E-mail:******@,:+82-2-961-9230,Fax:+82-2-961-9580??2019TheKoreanSocietyofAppliedPharmacology327BiomolTher27(3),327-335(2019)antioxidativefunction(Todaetal.,1985;al.,2010;MA,USA).Superoxidedismutase(SOD)assaykitandmalo-Canales-Aguirreetal.,2012).InEastAsiancountriesandIn-ndialdehyde(MDA)assaykitwerepurchasedfromCaymandia,ithasbeenusedasamedicationforimprovingdigestion,Chemical(AnnArbor,MI,USA).Aglutathione(GSH)-kitwaspurchasedfromBioVision(Mountainview,CA,USA).Allieshavesuggestedthatcurcumin,themajoractivepolyphe-,improvesmemoryandcogni-tivefunction(MishraandPalanivelu,2008;Yuetal.,2013).DrugadministrationHowever,curcuminhaslowbioavailability,anditsmechanismTheracurminwasadministratedto5XFADmiceonceadayofactionhasnotbeenclearlyelucidated(Anandetal.,2007).(100,300or1,000mg/kg,.)for12weeksfromtheageIfthebioavailabilityofcurcumincouldbeimproved,-matchedwild--(5mg/curminisanewlygeneratedformofcurcumin,whichisgener-kg),andparedNovelobjectrecognitiontestthatofcurcumin(Sasakietal.,2011).Therefore,TheracurminNovelobjectrecognitiontestconsistedofa2-dayhabitu-,atrainingsessionandaprobesession,asHere,weinvestigatedwhetherTheracurminamelioratesdescribedelsewhere(Kimetal.,2014).(5XFAD)(25×25×25cm)withoutThe5XFADmousehasamutationinhumanamyloidprecur-,themicewereplacedinthesameboxsorprotein(695)withtheSwedish(K670N,M671L),Floridawithoutanyobjectsfor2minandthenidenticalobjectswere(I716V),andLondon(V717I)andPSEN1(M146LandL286V)placedatthediagonaledgesofthesameboxesandthemicemutatations,-42proteinfrom6weeksofageandshowcognitiveimpair-theobjectswerecleanedwith70%ethanoltoremoveodorsmentatapproximately16weeks(Oakleyetal.,2006;.,2012).Inaddition,westudiedthemechanismofactionTheprobesessionwasperformed24hafterthetrainingses-ofTheraurminusingWesternblotandantioxidantactivityas-sion,,,-basedonEthoVisionsystem(Noldus,herland),andAnimalstheexplorationtimeofthenovelobject(Tnovel)andexplora-B6SJL-transgenic(APPSwFlLon,PSEN1*M146L*L286V)tiontimeofthefamiliarobject(Tfamiliar)-malemice(6-7weeks)werepurchasedfromJacksonLabo-criminationindexwascalculatedwiththefollowingequation:ratories(BarHarbor,ME,USA).Everymousewashousedin(Tnovel–Tfamiliar)/(Tnovel+Tfamiliar)×(lightsonat7:00AMandlightsoffatBarnesmazetest7:00PM).C57BL/6mice(6-7weeks)werepurchasedfromTheBarnesmazetestiswidelyusedtoexamineaspatialOrientBio(Seongnam,Korea)andusedasana?vecontrollearningandmemoryabilitywithlessstress(Barnes,1979;(23±1°C)andhumidity(60±10%)wereMorellini,2013).TheBarnesmazeisacircularplatform()-of20holesatregulardistances(5cmindiameter,38cmfrommitteethecenterand3cmfromtheedgeoftheplatform).Fourdif-(IACUC)ofKyungHeeUniversity((SE)-18-046).(6×12×6cm)wasinstalledunderoneoftheholesatafixedTheracurminwasdonatedbyHandokCo(Seoul,Korea).,inthepresenceTheracurmincontainscurcumin(30%)poundoflight,micewereplacedonthecenteroftheplatformandwithinavegitablegum(70%)(,themiceweregentlyguidedtoentertheescapebox,andLouise,MO,USA).Enhancedchemiluminescencereagentthentheentranceholewascoveredbyablackpolyvinylplas-waspurchasedfromGEHealthcareLifeSciences(Chicago,,USA).Mousemonoclonalanti-postsynapticprotein(PSD)Duringthe4daysoftrainingsessions,themicewereplaced95andanti-βactinantibodieswerepurchasedfromSantaintoapolyvinyltransparentcylinder(,15CruzBiotechnology(SantaCruz,CA,USA).Rabbitpolyclonalcminheight)thatwaslocatedatthecenteroftheplatformanti-synaptophysinandgoatpolyclonalanti--bindingadaptormolecule1(Iba-1)(Cambridge,UK).Vectorstainavidinbiotinyledescapeboxfor180s,andthetimethatittookforthemousetoplex(ABC)kitwerepurchasedfromVectorLabentertheescapeboxwasrecordedbyavideocamera-based(Burlingame,CA,USA).Apiercebicinchoninicacid(BCA)pro-EthoVisionsystem(Noldus)andwasrecordedastheescapeteinassaykitwaspurchasedfromThermoFisher(Waltham,,https:///.-DemenitaEffectsofTheracurminthemicewereguidedtoentertheescapebox,andlatencynol),,thelightwasimmediatelyturnedoff,(100,300or1,000mg/Threetrainingtiralswereperformedduringeachtrainingses-kg)for12weeks,themousewasimmediatelyperfusedwithsion,seperated20minintervalswhenthemiceweremovedtoPBS(50mM,)underisofluraneanesthesia,-,theescapeboxwasremoved,andaPBS(50mM,)andcentrifugedat7,,whichwasrecordedbyThen,-basedEthoVisionsystem(Noldus).ThetimeusedasenzymesourcetomeasuretheSODactivityandMDAspentineachofthequadrants,whichwerenamedleft,,thebrainwashomogenizedandoppositebasedonitspositionaroundthetargetquadrant,inglutathionereactionbufferandcentrifugedat10,,andtheextraproteinswereprecipitatedbyaddingsulfosali-(100,300or1,000mg/kg,.)andthebrainusingBCAproteinassaykit,,-(OPTIZEN2120UV,.,Daejeon,Korea).homogenizedinice-cold20mMTris-HClbuffer()con-taining1mMphenylmethylsulfonylfluoride(PMSF),1mMStatisticalanalysisorthovanadate,1mMsodiumfluoride,1mMEDTA,,Barnespleteproteaseinhibitor(1tabletper50mLmazetest,Westernblotanalysisandantioxidantactivityanal-ofbuffer).Thetissuehomogenateswerecentrifuged(4°C,ysiswereanalyzedbyone-wayanalysisofvariance(ANO-14,000rpm,20min),andthesupernatantswerecollectedandVA)withtheNewman-Keuls’-waythenquantifiedwiththeBCAproteinassaykit(Walker,1994).ANOVAfollowedbyBonferroni’sposthoctestwasusedtoTheproteinsamples(15μgofprotein)weresubjectedtoSDS-analyzetheobjectpreferenceratioduringthenovelobjectPAGE(8%or12%)-transferredtoPVDFmembranes(300mA,2h)±standarderrorbuffer(25mMTris-HClbuffercontaining192mMglycineandofthemean(SEM).Allstatisticalanalyseswereanalyzedwi