title: Defective microglial development in the hippocampus of Cx3cr1 deficient mice.
abstract: 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.
authors: Center for Life Nanoscience - Istituto Italiano di Tecnologia@Sapienza, Rome Italy.
authors: Francesca
authors: F
authors: Pagani
authors: Division of Psychiatry Research, University of Zürich, Zürich Switzerland ; Mouse Biology Unit, European Molecular Biology Laboratory, Monterotondo Italy.
authors: Rosa C
authors: RC
authors: Paolicelli
authors: Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome Italy.
authors: Emanuele
authors: E
authors: Murana
authors: Consiglio Nazionale delle Ricerche - Institute of Inorganic Methodologies and Plasmas, Department of Physics, Sapienza University of Rome, Rome Italy.
authors: Barbara
authors: B
authors: Cortese
authors: Center for Life Nanoscience - Istituto Italiano di Tecnologia@Sapienza, Rome Italy ; Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome Italy.
authors: Silvia
authors: S
authors: Di Angelantonio
authors: Department of Neuropathology, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
authors: Emanuele
authors: E
authors: Zurolo
authors: Mouse Biology Unit, European Molecular Biology Laboratory, Monterotondo Italy.
authors: Eva
authors: E
authors: Guiducci
authors: Mouse Biology Unit, European Molecular Biology Laboratory, Monterotondo Italy.
authors: Tiago A
authors: TA
authors: Ferreira
authors: Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome Italy.
authors: Stefano
authors: S
authors: Garofalo
authors: Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome Italy ; Istituto di Ricovero e Cura a Carattere Scientifico Neuromed Pozzilli, Italy.
authors: Myriam
authors: M
authors: Catalano
authors: Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome Italy ; Istituto di Ricovero e Cura a Carattere Scientifico Neuromed Pozzilli, Italy.
authors: Giuseppina
authors: G
authors: D'Alessandro
authors: Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome Rome, Italy.
authors: Alessandra
authors: A
authors: Porzia
authors: Center for Life Nanoscience - Istituto Italiano di Tecnologia@Sapienza, Rome Italy.
authors: Giovanna
authors: G
authors: Peruzzi
authors: Department of Experimental Medicine, Sapienza University of Rome Rome, Italy.
authors: Fabrizio
authors: F
authors: Mainiero
authors: Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome Italy ; Istituto di Ricovero e Cura a Carattere Scientifico Neuromed Pozzilli, Italy.
authors: Cristina
authors: C
authors: Limatola
authors: Mouse Biology Unit, European Molecular Biology Laboratory, Monterotondo Italy.
authors: Cornelius T
authors: CT
authors: Gross
authors: Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome Italy ; Istituto di Ricovero e Cura a Carattere Scientifico Neuromed Pozzilli, Italy.
authors: Davide
authors: D
authors: Ragozzino
keywords: CX3CR1; development; fractalkine; microglia; potassium currents; rearrangement