Effects of antenatal dexamethasone treatment on glucocorticoid receptor and calcyon gene expression in the prefrontal cortex of neonatal and adult common marmoset monkeys.docVIP

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Effects of antenatal dexamethasone treatment on glucocorticoid receptor and calcyon gene expression in the prefrontal cortex of neonatal and adult common marmoset monkeys.doc

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Effects of antenatal dexamethasone treatment on glucocorticoid receptor and calcyon gene expression in the prefrontal cortex of neonatal and adult common marmoset monkeys

DiazHeijtzetal.BehavioralandBrainFunctions2010,6:18 /content/6/1/18 RESEARCH OpenAccess Effectsofantenataldexamethasonetreatmenton glucocorticoidreceptorandcalcyongene expressionintheprefrontalcortexofneonatal andadultcommonmarmosetmonkeys RochellysDiazHeijtz1,2,3*,EberhardFuchs4,JoramFeldon5,ChristopherRPryce5,6,HansForssberg2,3 Abstract Background:Syntheticglucocorticoidssuchasdexamethasone(DEX)arecommonlyusedtopromotefetallung maturationinat-riskpretermbirths,butthereisemergingevidenceofsubsequentneurobehavioralabnormalities blemswithinattention/hyperactivity.However,molecularpathwaysmediatingeffectsof glucocorticoidoverexposureonmotorandcognitivedevelopmentarepoorlyunderstood. Methods:Inthisstudywithcommonmarmosetmonkeys,weinvestigatedforneonatalandadulthoodeffectsof antenatalDEXtreatmentontheexpressionofthecorticosteroidreceptorsandalsocalcyon,ariskgenefor attention-deficit/hyperactivitydisorder,intheprefrontalcortex(PFC).PregnantmarmosetswereexposedtoDEX (5mg/kgbodyweight)orvehicleduringearly(days42-48)orlate(days90-96)stagesofthe144-daypregnancy. Results:Inneonates,relativetocontrols,glucocorticoidreceptor(GR)mRNAlevelsweresignificantlyreducedafter thelateDEXtreatmentinthemedial,orbitalanddorsalPFCandaftertheearlyDEXtreatmentinthedorsalPFC. TheearlyDEXexposure,specifically,resultedinsignificantreductionincalcyonmRNAexpressioninthemedial, orbital,dorsalandlateralPFCrelativetocontrols.Mineralocorticoidreceptor(MR)mRNAlevelswerenot significantlyaffectedbyDEXtreatment.Inadults,PFCGR,calcyon,andMRmRNAlevelswerenotsignificantly affectedbyearlyorlateprenatalDEXtreatment. Conclusion:ThesefindingsindicatethatantenatalDEXtreatmentcouldleadtoshort-termalterationsinPFC expressionoftheGRandcalcyongenes,withpossibleneurodevelopmentalfunctionalconsequences. Background glucocorticoids prenatally could disturb normal brain Epidemiological studies indicate that children exposed development[3].Thisisbecausethehumanfetalbrain to elevated levels of glucocorticoids during fetal