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., Paolicelli, R.c., Murana, E., Cortese, B., DI ANGELANTONIO, S., Zurolo, E., Guiducci, E., Ferreira, T.a., Garofalo, S., Catalano, M., D'Alessandro, G., Porzia, A., Peruzzi, G., Mainiero, F., Limatola, C., Gross, C.t., Ragozzino, D.A.. - 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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