简介：MaleWistar7-day-oldratswereinjectedwith40mg/kgketamineintraperitoneally,followedbythreeadditionalinjectionsof20mg/kgketamineeachuponrestorationoftherightingreflex.Neonatalratsinjectedwithequivalentvolumesofsalineservedascontrols.Hippocampalsampleswerecollectedat1,7or14daysfollowingadministration.Electronmicroscopyshowedthatneuronalstructurechangednoticeablyfollowingketaminetreatment.Specifically,microtubularstructurebecameirregularanddisorganized.Quantitativerealtime-PCRrevealedthatphosphorylatedtaumRNAwasupregulatedafterketamine.Westernblotanalysisdemonstratedthatphosphorylatedtaulevelsatserine396initiallydecreasedat1dayafterketamineinjection,andthengraduallyreturnedtocontrolvalues.At14daysafterinjection,levelsofphosphorylatedtauwerehigherintheketaminegroupthaninthecontrolgroup.Tauproteinphosphorylatedatserine404significantlyincreasedafterketamineinjection,andthengraduallydecreasedwithtime.However,thelevelsoftauproteinatserine404weresignificantlygreaterintheketaminegroupthaninthecontrolgroupuntil14days.ThepresentresultsindicatethatketamineinducesanincreaseofphosphorylatedtaumRNAandexcessivephosphorylationoftauproteinatserine404,causingdisruptionofmicrotubulesintheneonatalrathippocampusandpotentiallyresultingindamagetohippocampalneurons.