EffectofdevelopmentalleadexposureontheexpressionofspecificNMDAreceptorsubunitmRNAsinthehippocampusofneonatalratsbydigoxigenin-labeledinsituhybridizationhistochemistryXiao-yanZhang,Ai-PingLiu,Di-YunRuan*,JinLiuSchoolofLifeScience,UniversityofScienceandTechnologyofChina,Hefei,Anhui230026,ChinaReceived13July2001;receivedinrevisedform5September2001;accepted15November2001AbstractTheN-methyl-D-aspartate(NMDA)receptorhasanimportantroleinlearningandmemory.Inthisstudy,theeffectsofchronicPbexposureonNMDAreceptorsubunitmRNAsexpressioninthedevelopingrathippocampuswereexaminedbydigoxigenin(DIG)-labeledinsituhybridization.InPb-exposedrats,hippocampalNR1-2amRNAlevelsweresignificantlyincreasedinCA1,CA4andDGsubfieldsat15daysofageandCA4andDGsubfieldsat20daysofage.Thelead(Pb)exposureresultedinasignificantincreaseofNR2DmRNAlevelsinCA1,CA2,CA4andDGhippocampalsubfieldsat20daysofage.HippocampalNR2AmRNAlevelsweresignificantlydecreasedinCA1,CA2,CA3andDGsubfieldsfrom15-day-oldPb-exposedratsandCA1,CA3andDGsubfieldsfrom20-day-oldPb-exposedrats.HippocampalNR3AmRNAlevelswerealsosignificantlydecreasedinCA1,CA4andDGsubfieldsat15daysofageandCA1andDGsubfieldsat20daysofageinPb-exposedrats.ThePb-inducedsubunitspecificchangesinhippocampalNMDAreceptorsubunitmRNAexpressionmayleadtoabnormalityofnaturalNMDAstoichiometryandinterferewiththephysiologicalfunctionoftheNMDAreceptorinthedevelopmentofdefinedneuronalconnections.D2002ElsevierScienceInc.Allrightsreserved.Keywords:Lead;NMDAreceptorsubunitmRNA;Rathippocampus1.IntroductionNeuronalplasticityassociatedwithlearning,memoryanddevelopmentiscontrolled,inpart,byN-methyl-D-aspartate(NMDA)receptors[8,38,54].ExcessiveactivationofNMDAreceptorstriggersmechanismsleadingtonervecelldeath,electrographicseizures[38]andavarietyofneuro-degenerativediseases[47].ItiscurrentlybelievedthattheNMDAreceptorisaheteromultimericchannelcomprisingtheubiquitousNMDAR1(NR1)subunitandatleastoneregionallylocal-izedNMDAR2(NR2)subunit[21].Recentstudies[26,36]showedthatNMDAreceptorscontain...
