Administration of Dexamethasone to Neonatal Rats Induces Hypomyelination and Changes in the Morphology of Oligodendrocyte Precursors

摘要

Toexaminewhetherhypomyelinationinneonatalratsmightberelatedtoapoptosisofoligodendrocyteprogenitors,weadministereddexamethasone(0.5mg/kgSC)toneonatalratsonpostnatal(P)days1through5.ImmunofluorescentstainingandWesternblottingformyelinbasicprotein(MBP)wereperformedonP14.MorphologicchangesassociatedwithapoptoticdeathofoligodendrocyteprogenitorswereassessedbyusingimmunofluorescentstainingonP5ofsurfacemarkerspresentatdifferentdevelopmentalstagesofoligodendrocyteprogenitors(O4andO1)andbydouble-stainingwithterminaldeoxynucleotidyltransferase-mediateddigoxigenin#8211;dUTPnickend-labeling(TUNEL)andO4orO1.AdministrationofdexamethasonetoneonatalratsreducedtheexpressionofMBPinthewhitematterbyP14.Inaddition,dexamethasonereducedtheexpressionofO4-positivecells,presumablypreoligodendrocytes,inthecorpuscallosumandinduceddegenerativechanges,suchascytoplasmiccondensationandfragmented,tortuousprocesses,inoligodendrocyteprogenitors,andincreasedthenumberofTUNEL-positivepyknoticnucleiofoligodendrocyteprogenitors.Thesefindingssuggestthatthedexamethasone-induceddecreasedexpressionofMBPinthecerebralhemispheresoftheneonatalratsisduetoapoptoticdegenerationofoligodendrocyteprogenitors.Administrationofdexamethasoneduringthecriticalperiodofbraindevelopmentmayincreasetheriskofapoptosisinoligodendrocyteprogenitors,subsequentlyresultinginhypomyelination.