Effects of bone morphogenetic protein-4 on spatial memory and cholinergic expression in the dentate gyrus after fornix-fimbria transection in rats

(整期优先)网络出版时间:2008-01-11
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BACKGROUND:Previousexperimentshaveconfirmedbonemorphogeneticproteins(BMPs)upregulatecholinergicexpressioninneuronsisolatedfromtheembryonicrathippocampusandcerebralcortex.Therefore,BMPscouldbeusefulfortreatingAlzheimer'sdiseaseandotherneurodegenerativediseases.OBJECTIVE:BMP-4wasinfusedintothehippocampaldentategyrusoffornix-fimbriatransectedratstotesttheeffectsofBMP-4oncholinergicexpressionindentategyrusneurons,andtoobservechangesinspatialmemorybehavior.DESIGN:Arandomizedcontrolledanimalexperiment.SETTING:DepartmentofNeurosurgeryandLaboratoryforCellBiology,InstituteofGeriatrics,GeneralHospitalofChinesePLA.MATERIALS:Twenty-sevenhealthyadultmaleSpragueDawley(SD)rats,weighing250-300g,wereprovidedbytheLaboratoryAnimalCenteroftheGeneralHospitalofChinesePLA.Reagents:BMP-4(B-2680,SigmaCompany)andcholineacetyltransferase(ChAT)antibody(AB5042,ChemiconCompany)wereusedinthisstudy.Equipments:aratstereotaxicinstrument(type:SN-2N,NarushigeGroup,Japan)andImage-prog-plusimageanalysissoftware(MediaCyberneticscompany,USA)wereusedinthisstudy.Theprotocolwascarriedoutinaccordancewithethicalguidelinesfortheuseandcareofanimals.METHODS:ThisexperimentwasperformedintheInstituteofGeriatrics,GeneralHospitalofChinesePLAbetweenJuly2004andMarch2005.Ratswererandomlypidedinto4groups:Alzheimer'sdiseasegroup(n=7),normalcontrolgroup(n=5),BMP-4-Alzheimer'sdiseasegroup(n=8),andmodelgroup(n=7).IntheAlzheimer'sdiseasegroup,thelefthippocampalfornix-fimbriaofratswastransectedtomimicAlzheimer'sdiseasesymptoms.IntheBMP-4-Alzheimer'sdiseasegroup,1μLBMP-4(10mg/L)wasperfusedintotheleftdentategyruswithamicroinjectorat1μL/min.Inthemodelgroup,1μLsalinewasperfusedintothesamepositionbythesamemethod.Twenty-eightdaysafterinjection,Morriswatermazetestwasperformedinallr