Role of CEBPβ Transcription Factor in Adult Hippocampal Neurogenesis 英文参考文献.docVIP

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Role of CEBPβ Transcription Factor in Adult Hippocampal Neurogenesis 英文参考文献.doc

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Role of CEBPβ Transcription Factor in Adult Hippocampal Neurogenesis 英文参考文献

RoleofC/EBPbTranscriptionFactorinAdult HippocampalNeurogenesis MartaCortes-Canteli1,2¤,DianaAguilar-Morante1,2,MarinaSanz-SanCristobal1,2,DiegoMegias3 ,Angel Santos4,AnaPerez-Castillo1,2* 1InstitutodeInvestigacionesBiomedicas‘‘AlbertoSols’’,ConsejoSuperiordeInvestigacionesCientificas-UniversidadAutonomadeMadrid,Madrid,Spain,2Centrode Investigacio′nBiome′dica enRedsobreEnfermedadesNeurodegenerativas(CIBERNED),Madrid,Spain,3CentroNacionaldeInvestigacionesOncologicas,Madrid,Spain, 4DepartamentodeBioquimicayBiologiaMolecular,FacultaddeMedicina,UniversidadComplutensedeMadrid,Madrid,Spain Abstract Background:Thedentategyrusofthehippocampusisoneoftheregionsinwhichneurogenesistakesplaceintheadult brain.WehavepreviouslydemonstratedthatCCAAT/enhancerbindingproteinb(C/EBPb)isexpressedinthegranularlayer of the dentate gyrus of the adult mouse hippocampus. Taking into account the important role of C/EBPb in the consolidationoflongtermmemory,thefactthatnewbornneuronsinthehippocampuscontributetolearningandmemory processes, and the role of this transcription factor, previously demonstrated by our group, in regulating neuronal differentiation,wespeculatedthatthistranscriptionfactorcouldregulatestem/progenitorcellsinthisregionofthebrain. Methodology/PrincipalFindings:Here,weshow,usingC/EBPbknockoutmice,thatC/EBPbexpressionisobservedinthe subsetofnewborncellsthatproliferateinthehippocampusoftheadultbrain.MicelackingC/EBPbpresentreducedsurvival of newborn cells in the hippocampus, a decrease in the number of these cells that differentiate into neurons and a diminishednumberofcellsthatareproliferatinginthesubgranularzoneofthedentategyrus.Theseresultswerefurther confirmed in vitro. Neurosphere cultures from adult mice deficient in C/EBPb present less proliferation and neuronal differentiationthanneurospheresderivedfromwildtypemice. Conclusions/Significance:Insummary,usinginvivoandinvitrostrategies,wehaveidentifiedC/EBPbasakeyplayerinthe proliferationandsurvivalofthenewneuronsproducedin