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, Francesca; Paolicelli, Rc; Murana, Emanuele; Cortese, B; DI ANGELANTONIO, Silvia; Zurolo, E; Guiducci, E; Ferreira, Ta; Garofalo, Stefano; Catalano, Myriam; D'Alessandro, Giuseppina; Porzia, Alessandra; Peruzzi, Giovanna; Mainiero, Fabrizio; Limatola, Cristina; Gross, Ct; Ragozzino, Davide Antonio. - In: FRONTIERS IN CELLULAR NEUROSCIENCE. - ISSN 1662-5102. - ELETTRONICO. - 9:(2015). [10.3389/fncel.2015.00111]
Defective microglial development in the hippocampus of Cx3cr1 deficient mice
PAGANI, FRANCESCA;MURANA, EMANUELE;DI ANGELANTONIO, SILVIA;GAROFALO, STEFANO;CATALANO, Myriam;D'ALESSANDRO, GIUSEPPINA;PORZIA, Alessandra;PERUZZI, Giovanna;MAINIERO, Fabrizio;LIMATOLA, Cristina;RAGOZZINO, Davide Antonio
2015
Abstract
Microglialcellsparticipateinbraindevelopmentandinfluenceneuronallossandsynapticmaturation.Fractalkineisanimportantneuronalchemokinewhoseexpressionincreasesduringdevelopmentandthatcaninfluencemicrogliafunctionviathefractalkinereceptor,CX3CR1.MicelackingCx3cr1showavarietyofneuronaldefectsthoughttobetheresultofdeficientmicrogliafunction.ActivationofCX3CR1isimportantforthepropermigrationofmicrogliatositesofinjuryandintothebrainduringdevelopment.However,littleisknownabouthowfractalkinemodulatesmicroglialpropertiesduringdevelopment.Hereweexaminedmicroglialmorphology,responsetoATP,andK+currentpropertiesinacutebrainslicesfromCx3cr1knockoutmiceacrosspostnatalhippocampaldevelopment.Wefoundthatfractalkinesignalingisnecessaryforthedevelopmentofseveralmorphologicalandphysiologicalfeaturesofmicroglia.Specifically,wefoundthattheoccurrenceofanoutwardrectifyingK+current,typicalofactivatedmicroglia,thatpeakedduringthesecondandthirdpostnatalweek,wasreducedinCx3cr1knockoutmice.FractalkinesignalingalsoinfluencedmicroglialmorphologyandabilitytoextendprocessesinresponsetoATPfollowingitsfocalapplicationtotheslice.Ourresultsrevealthedevelopmentalprofileofseveralmorphologicalandphysiologicalpropertiesofmicrogliaanddemonstratethattheseprocessesaremodulatedbyfractalkinesignaling.| File | Dimensione | Formato | |
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