Microglialcellsparticipateinbraindevelopmentandinfluenceneuronallossandsynapticmaturation.Fractalkineisanimportantneuronalchemokinewhoseexpressionincreasesduringdevelopmentandthatcaninfluencemicrogliafunctionviathefractalkinereceptor,CX3CR1.MicelackingCx3cr1showavarietyofneuronaldefectsthoughttobetheresultofdeficientmicrogliafunction.ActivationofCX3CR1isimportantforthepropermigrationofmicrogliatositesofinjuryandintothebrainduringdevelopment.However,littleisknownabouthowfractalkinemodulatesmicroglialpropertiesduringdevelopment.Hereweexaminedmicroglialmorphology,responsetoATP,andK+currentpropertiesinacutebrainslicesfromCx3cr1knockoutmiceacrosspostnatalhippocampaldevelopment.Wefoundthatfractalkinesignalingisnecessaryforthedevelopmentofseveralmorphologicalandphysiologicalfeaturesofmicroglia.Specifically,wefoundthattheoccurrenceofanoutwardrectifyingK+current,typicalofactivatedmicroglia,thatpeakedduringthesecondandthirdpostnatalweek,wasreducedinCx3cr1knockoutmice.FractalkinesignalingalsoinfluencedmicroglialmorphologyandabilitytoextendprocessesinresponsetoATPfollowingitsfocalapplicationtotheslice.Ourresultsrevealthedevelopmentalprofileofseveralmorphologicalandphysiologicalpropertiesofmicrogliaanddemonstratethattheseprocessesaremodulatedbyfractalkinesignaling.
Defective microglial development in the hippocampus of Cx3cr1 deficient mice
Pagani F;Cortese B;
2015
Abstract
Microglialcellsparticipateinbraindevelopmentandinfluenceneuronallossandsynapticmaturation.Fractalkineisanimportantneuronalchemokinewhoseexpressionincreasesduringdevelopmentandthatcaninfluencemicrogliafunctionviathefractalkinereceptor,CX3CR1.MicelackingCx3cr1showavarietyofneuronaldefectsthoughttobetheresultofdeficientmicrogliafunction.ActivationofCX3CR1isimportantforthepropermigrationofmicrogliatositesofinjuryandintothebrainduringdevelopment.However,littleisknownabouthowfractalkinemodulatesmicroglialpropertiesduringdevelopment.Hereweexaminedmicroglialmorphology,responsetoATP,andK+currentpropertiesinacutebrainslicesfromCx3cr1knockoutmiceacrosspostnatalhippocampaldevelopment.Wefoundthatfractalkinesignalingisnecessaryforthedevelopmentofseveralmorphologicalandphysiologicalfeaturesofmicroglia.Specifically,wefoundthattheoccurrenceofanoutwardrectifyingK+current,typicalofactivatedmicroglia,thatpeakedduringthesecondandthirdpostnatalweek,wasreducedinCx3cr1knockoutmice.FractalkinesignalingalsoinfluencedmicroglialmorphologyandabilitytoextendprocessesinresponsetoATPfollowingitsfocalapplicationtotheslice.Ourresultsrevealthedevelopmentalprofileofseveralmorphologicalandphysiologicalpropertiesofmicrogliaanddemonstratethattheseprocessesaremodulatedbyfractalkinesignaling.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.