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Antenatal Glucocorticoid Treatment Affects Hippocampal Development in Mice.doc

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Antenatal Glucocorticoid Treatment Affects Hippocampal Development in Mice

AntenatalGlucocorticoidTreatmentAffects HippocampalDevelopmentinMice CornelleW.Noorlander1,2,DeodataTijsseling2*,EllenV.S.Hessel1,WillemB.deVries3,JanB.Derks2, GerardH.A.Visser2.,PierreN.E.deGraan1. 1BrainCenterRudolfMagnus,DepartmentofNeuroscienceandPharmacology,UniversityMedicalCenterUtrecht,Utrecht,TheNetherlands,2DepartmentofObstetrics, UniversityMedicalCenterUtrecht,Utrecht,TheNetherlands,3DepartmentofNeonatology,UniversityMedicalCenterUtrecht,Utrecht,TheNetherlands Abstract Synthetic glucocorticoids are administered to pregnant women at risk for preterm delivery, to enhance fetal lung maturation.Thebenefitofthistreatmentiswellestablished,howevercautionisnecessarybecauseofpossibleunwanted side effects on development of different organ systems, including thebrain. Actions of glucocorticoids are mediated by corticosteroidreceptors,whicharehighlyexpressedinthehippocampus,abrainstructureinvolvedincognitivefunctions. Therefore, we analyzed the effects of a single antenatal dexamethasone treatment on the development of the mouse hippocampus.Aclinicallyrelevantdoseofdexamethasone(0.4mg/kg)wasadministeredtopregnantmiceatembryonic day 15.5 and the hippocampus was analyzed from embryonic day 16 until adulthood. We investigated the effects of dexamethasonetreatmentonanatomicalchanges,apoptosisandproliferationinthehippocampus,hippocampalvolume andontotalbodyweight.Ourresultsshowthatdexamethasonetreatmentreducedbodyweightandhippocampalvolume transiently during development, but these effects were no longer detected at adulthood. Dexamethasone treatment increased the number of apoptotic cells in the hippocampus until birth, but postnatally no effects of dexamethasone treatmenton apoptosis werefound. Duringthephasewith increased apoptosis,dexamethasonetreatment reducedthe numberofproliferatingcellsinthesubgranularzoneofthedentategyrus.Thenumberofproliferativecellswasincreasedat postnatalday5and10,butwasdecreasedagainattheadultstage.Thislatterlong-termandnegativeeffectofant