Expression of the Axonal Membrane Glycoprotein M6a Is Regulated by Chronic Stress 英文参考文献.docVIP

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Expression of the Axonal Membrane Glycoprotein M6a Is Regulated by Chronic Stress 英文参考文献.doc

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Expression of the Axonal Membrane Glycoprotein M6a Is Regulated by Chronic Stress 英文参考文献

ExpressionoftheAxonalMembraneGlycoproteinM6aIs RegulatedbyChronicStress BenCooper1¤,EberhardFuchs1,2,3*,GabrieleFlu¨gge1,3 1Clinical Neurobiology Laboratory, German Primate Center, Leibniz Institute for Primate Research, Go¨ttingen, Germany, 2Department of Neurology, Medical School, UniversityofGo¨ttingen,Go¨ttingen,Germany,3DFGResearchCenterMolecularPhysiologyoftheBrain(CMPB),UniversityofGo¨ttingen,Go¨ttingen,Germany Abstract It has been repeatedly shown that chronic stress changes dendrites, spines and modulates expression of synaptic molecules.Theseeffectsallmayimpairinformationtransferbetweenneurons.Thepresentstudyshowsthatchronicstress alsoregulatesexpressionofM6a,aglycoproteinwhichislocalisedinaxonalmembranes.Wehavepreviouslydemonstrated thatM6aisacomponentofglutamatergicaxons.ThepresentdatarevealthatitisthesplicevariantM6a-Ib,notM6a-Ia, whichisstronglyexpressedinthebrain.Chronicstressinmalerats(3weeksdailyrestraint)hasregionaleffects:quantitative insituhybridizationdemonstratedthatM6a-IbmRNAindentategyrusgranuleneuronsandinCA3pyramidalneuronsis downregulated,whereasM6a-IbmRNAinthemedialprefrontalcortexisupregulatedbychronicstress.Thisisthefirststudy showingthatexpressionofanaxonalmembranemoleculeisdifferentiallyaffectedbystressinaregion-dependentmanner. Therefore,onemayspeculatethatdiminishedexpressionoftheglycoproteininthehippocampusleadstoalteredoutputin thecorrespondingcorticalprojectionareas.EnhancedM6a-Ibexpressioninthemedialprefrontalcortex(inareasprelimbic andinfralimbiccortex)mightbeinterpretedasacompensatorymechanisminresponsetochangesinaxonalprojections fromthehippocampus.Ourfindingsprovideevidencethatinadditiontoalterationsindendritesandspineschronicstress alsochangestheintegrityofaxonsandmaythusimpairinformationtransferevenbetweendistantbrainregions. Citation: Cooper B, Fuchs E, Flu¨gge G (2009) Expression of the Axonal Membrane Glycoprotein M6a Is Regulated by Chronic Stress. PLoS ONE 4(1): e3659. doi:10.1371/journal.pone.0003659 Editor:Bernhar