Defective microglial development in the hippocampus of Cx3cr1 deficient mice

Microglial cells participate in brain development and influence neuronal loss and synaptic maturation. Fractalkine is an important neuronal chemokine whose expression increases during development and that can influence microglia function via the fractalkine receptor, CX3CR1. Mice lacking Cx3cr1 show...

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Main Authors: Francesca ePagani, Rosa ePaolicelli, Emanuele eMurana, Barbara eCortese, Silvia eDi Angelantonio, Emanuele eZurolo, Eva eGuiducci, Tiago A. eFerreira, Stefano eGarofalo, Myriam eCatalano, Giuseppina eD'Alessandro, Alessandra ePorzia, Giovanna ePeruzzi, Fabrizio eMainiero, Cristina eLimatola, Cornelius eGross, Davide eRagozzino
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-03-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00111/full
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author Francesca ePagani
Rosa ePaolicelli
Rosa ePaolicelli
Emanuele eMurana
Barbara eCortese
Silvia eDi Angelantonio
Silvia eDi Angelantonio
Emanuele eZurolo
Eva eGuiducci
Tiago A. eFerreira
Stefano eGarofalo
Myriam eCatalano
Myriam eCatalano
Giuseppina eD'Alessandro
Alessandra ePorzia
Giovanna ePeruzzi
Fabrizio eMainiero
Cristina eLimatola
Cristina eLimatola
Cornelius eGross
Davide eRagozzino
Davide eRagozzino
author_facet Francesca ePagani
Rosa ePaolicelli
Rosa ePaolicelli
Emanuele eMurana
Barbara eCortese
Silvia eDi Angelantonio
Silvia eDi Angelantonio
Emanuele eZurolo
Eva eGuiducci
Tiago A. eFerreira
Stefano eGarofalo
Myriam eCatalano
Myriam eCatalano
Giuseppina eD'Alessandro
Alessandra ePorzia
Giovanna ePeruzzi
Fabrizio eMainiero
Cristina eLimatola
Cristina eLimatola
Cornelius eGross
Davide eRagozzino
Davide eRagozzino
author_sort Francesca ePagani
collection DOAJ
description Microglial cells participate in brain development and influence neuronal loss and synaptic maturation. Fractalkine is an important neuronal chemokine whose expression increases during development and that can influence microglia function via the fractalkine receptor, CX3CR1. Mice lacking Cx3cr1 show a variety of neuronal defects thought to be the result of deficient microglia function. Activation of CX3CR1 is important for the proper migration of microglia to sites of injury and into the brain during development. However, little is known about how fractalkine modulates microglial properties during development. Here we examined microglial morphology, response to ATP, and K+ current properties in acute brain slices from Cx3cr1 knockout mice across postnatal hippocampal development. We found that fractalkine signaling is necessary for the development of several morphological and physiological features of microglia. Specifically, we found that the occurrence of an outward rectifying K+ current, typical of activated microglia, that peaked during the second and third postnatal week, was reduced in Cx3cr1 knockout mice. Fractalkine signaling also influenced microglial morphology and ability to extend processes in response to ATP following its focal application to the slice. Our results reveal the developmental profile of several morphological and physiological properties of microglia and demonstrate that these processes are modulated by fractalkine signaling.
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spelling doaj.art-8cb62bfc85f44604bac75c98f5f020fe2022-12-22T01:38:44ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022015-03-01910.3389/fncel.2015.00111133241Defective microglial development in the hippocampus of Cx3cr1 deficient miceFrancesca ePagani0Rosa ePaolicelli1Rosa ePaolicelli2Emanuele eMurana3Barbara eCortese4Silvia eDi Angelantonio5Silvia eDi Angelantonio6Emanuele eZurolo7Eva eGuiducci8Tiago A. eFerreira9Stefano eGarofalo10Myriam eCatalano11Myriam eCatalano12Giuseppina eD'Alessandro13Alessandra ePorzia14Giovanna ePeruzzi15Fabrizio eMainiero16Cristina eLimatola17Cristina eLimatola18Cornelius eGross19Davide eRagozzino20Davide eRagozzino21Istituto Italiano di TecnologiaUniversity of ZürichEuropean Molecular Biology LaboratoryIstituto Pasteur-Fondazione Cenci BolognettiSapienza University of RomeIstituto Italiano di TecnologiaIstituto Pasteur-Fondazione Cenci BolognettiUniversity of AmsterdamEuropean Molecular Biology LaboratoryEuropean Molecular Biology LaboratoryIstituto Pasteur-Fondazione Cenci BolognettiIstituto Pasteur-Fondazione Cenci BolognettiIRCCS NeuromedIstituto Pasteur-Fondazione Cenci BolognettiIstituto Pasteur-Fondazione Cenci BolognettiIstituto Italiano di TecnologiaSapienza University of RomeIstituto Pasteur-Fondazione Cenci BolognettiIRCCS NeuromedEuropean Molecular Biology LaboratoryEuropean Molecular Biology LaboratoryIRCCS NeuromedMicroglial cells participate in brain development and influence neuronal loss and synaptic maturation. Fractalkine is an important neuronal chemokine whose expression increases during development and that can influence microglia function via the fractalkine receptor, CX3CR1. Mice lacking Cx3cr1 show a variety of neuronal defects thought to be the result of deficient microglia function. Activation of CX3CR1 is important for the proper migration of microglia to sites of injury and into the brain during development. However, little is known about how fractalkine modulates microglial properties during development. Here we examined microglial morphology, response to ATP, and K+ current properties in acute brain slices from Cx3cr1 knockout mice across postnatal hippocampal development. We found that fractalkine signaling is necessary for the development of several morphological and physiological features of microglia. Specifically, we found that the occurrence of an outward rectifying K+ current, typical of activated microglia, that peaked during the second and third postnatal week, was reduced in Cx3cr1 knockout mice. Fractalkine signaling also influenced microglial morphology and ability to extend processes in response to ATP following its focal application to the slice. Our results reveal the developmental profile of several morphological and physiological properties of microglia and demonstrate that these processes are modulated by fractalkine signaling.http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00111/fullMicrogliadevelopmentrearrangementFractalkineCX3CR1potassium currents
spellingShingle Francesca ePagani
Rosa ePaolicelli
Rosa ePaolicelli
Emanuele eMurana
Barbara eCortese
Silvia eDi Angelantonio
Silvia eDi Angelantonio
Emanuele eZurolo
Eva eGuiducci
Tiago A. eFerreira
Stefano eGarofalo
Myriam eCatalano
Myriam eCatalano
Giuseppina eD'Alessandro
Alessandra ePorzia
Giovanna ePeruzzi
Fabrizio eMainiero
Cristina eLimatola
Cristina eLimatola
Cornelius eGross
Davide eRagozzino
Davide eRagozzino
Defective microglial development in the hippocampus of Cx3cr1 deficient mice
Frontiers in Cellular Neuroscience
Microglia
development
rearrangement
Fractalkine
CX3CR1
potassium currents
title Defective microglial development in the hippocampus of Cx3cr1 deficient mice
title_full Defective microglial development in the hippocampus of Cx3cr1 deficient mice
title_fullStr Defective microglial development in the hippocampus of Cx3cr1 deficient mice
title_full_unstemmed Defective microglial development in the hippocampus of Cx3cr1 deficient mice
title_short Defective microglial development in the hippocampus of Cx3cr1 deficient mice
title_sort defective microglial development in the hippocampus of cx3cr1 deficient mice
topic Microglia
development
rearrangement
Fractalkine
CX3CR1
potassium currents
url http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00111/full
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