Wnt1/β-cateninsignalingup-regulatesspinalVGLUT2expressiontomaintainneuropathicpaininmice

摘要： OBJECTIVEThepresentstudywasaimedtoinvestigatetheroleofWnt/β-cateninsig.nalinginspinalVGLUT2regulationandneuropathicpain.METHODSToelucidatetheassociationbe.tweenVGLUT2andneuropathicpain,wedeterminedtheexpressionanddistributioncharacteristicsofVGLUT2inmicesubjectedtosparednerveinjury(SNI),andthenobservedtheeffectsoftwoVGLUT2targetingshRNAsonmechanicalallodyniaandglutamaterelease.TheeffectsofWnt/β-cateninsignal.ingonVGLUT2expressionandpainbehaviorwereinvestigatedbyusingWntagonist,Wnt1,andWnt/β-cateninpathwayinhibitorXAV939inSNImice.RESULTSSNIsurgeryinducedsignificantup-regula.tionofVGLUT2onpostoperativedays7,14,and21.DoubleimmunofluorescencelabelingofVGLUT2withNeuN,MAP2,Iba-1,orGFAPshowedthatVGLUT2wasmainlyexpressedinneuronsinthedor.salhornofthespinalcordafterSNI(NeuN,MAP2).IntrathecaladministrationofVGLUT2shRNAsbe.foreorafterSNIsurgerysignificantlydecreasedmechanicalallodyniaandglutamaterelease.Mean.while,Wnt1/β-cateninsignalingincreasedsignificantlyafterSNIsurgery.Over-expressionofβ-catenininPC12cellsincreasedVGLUT2proteinlevel,intrathecaladministrationofWntagonistorWnt1signifi.cantlyincreasedVGLUT2proteinexpressioninspinalcord,whileWnt/β-cateninpathwayinhibitorXAV939decreasedVGLUT2expressioninPC12cellsandspinalcord.Additionally,intrathecaladmin.istrationofXAV9397daysafterSNIsignificantlyattenuatedmechanicalallodyniainmice,whichwasinaccordancewithdown-regulationofVGLUT2proteinlevels.VGLUT2shRNAssignificantlyattenuat.edWntagonistorWnt1inducedmechanicalallodynia.CONCLUSIONWnt1/β-cateninsignalingpath.wayup-regu-latesthespinalVGLUT2expression,andthisregulationisinvolvedinneuropathicpainbehavior. ... （共1页）