Fractalkine Modulates Microglia Metabolism in Brain Ischemia
In the CNS, the chemokine CX3CL1 (fractalkine) is expressed on neurons while its specific receptor CX3CR1 is expressed on microglia and macrophages. Microglia play an important role in health and disease through CX3CL1/CX3CR1 signaling, and in many neurodegenerative disorders, microglia dysregulatio...
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doaj-db9cc470559f424087f6c38352523bc22020-11-25T00:44:56ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-09-011310.3389/fncel.2019.00414451695Fractalkine Modulates Microglia Metabolism in Brain IschemiaClotilde Lauro0Giuseppina Chece1Lucia Monaco2Fabrizio Antonangeli3Giovanna Peruzzi4Serena Rinaldo5Alessio Paone6Francesca Cutruzzolà7Cristina Limatola8Cristina Limatola9Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, Rome, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Medicine, Laboratory Affiliated to Istituto Pasteur Italia – Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, ItalyCenter for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome, ItalyDepartment of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Rome, ItalyDepartment of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Rome, ItalyDepartment of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Rome, ItalyDepartment of Physiology and Pharmacology, Laboratory Affiliated to Istituto Pasteur Italia – Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, ItalyIRCCS NeuroMed, Pozzilli, ItalyIn the CNS, the chemokine CX3CL1 (fractalkine) is expressed on neurons while its specific receptor CX3CR1 is expressed on microglia and macrophages. Microglia play an important role in health and disease through CX3CL1/CX3CR1 signaling, and in many neurodegenerative disorders, microglia dysregulation has been associated with neuro-inflammation. We have previously shown that CX3CL1 has neuroprotective effects against cerebral ischemia injury. Here, we investigated the involvement of CX3CL1 in the modulation of microglia phenotype and the underlying neuroprotective effect on ischemia injury. The expression profiles of anti- and pro-inflammatory genes showed that CX3CL1 markedly inhibited microglial activation both in vitro and in vivo after permanent middle cerebral artery occlusion (pMCAO), accompanied by an increase in the expression of anti-inflammatory genes. Moreover, CX3CL1 induces a metabolic switch in microglial cells with an increase in the expression of genes related to the oxidative pathway and a reduction in those related to the glycolytic pathway, which is the metabolic state associated to the pro-inflammatory phenotype for energy production. The data reported in this paper suggest that CX3CL1 protects against cerebral ischemia modulating the activation state of microglia and its metabolism in order to restrain inflammation and organize a neuroprotective response against the ischemic insult.https://www.frontiersin.org/article/10.3389/fncel.2019.00414/fullCX3CL1microgliaischemianeuroprotectionneuroinflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Clotilde Lauro Giuseppina Chece Lucia Monaco Fabrizio Antonangeli Giovanna Peruzzi Serena Rinaldo Alessio Paone Francesca Cutruzzolà Cristina Limatola Cristina Limatola |
spellingShingle |
Clotilde Lauro Giuseppina Chece Lucia Monaco Fabrizio Antonangeli Giovanna Peruzzi Serena Rinaldo Alessio Paone Francesca Cutruzzolà Cristina Limatola Cristina Limatola Fractalkine Modulates Microglia Metabolism in Brain Ischemia Frontiers in Cellular Neuroscience CX3CL1 microglia ischemia neuroprotection neuroinflammation |
author_facet |
Clotilde Lauro Giuseppina Chece Lucia Monaco Fabrizio Antonangeli Giovanna Peruzzi Serena Rinaldo Alessio Paone Francesca Cutruzzolà Cristina Limatola Cristina Limatola |
author_sort |
Clotilde Lauro |
title |
Fractalkine Modulates Microglia Metabolism in Brain Ischemia |
title_short |
Fractalkine Modulates Microglia Metabolism in Brain Ischemia |
title_full |
Fractalkine Modulates Microglia Metabolism in Brain Ischemia |
title_fullStr |
Fractalkine Modulates Microglia Metabolism in Brain Ischemia |
title_full_unstemmed |
Fractalkine Modulates Microglia Metabolism in Brain Ischemia |
title_sort |
fractalkine modulates microglia metabolism in brain ischemia |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2019-09-01 |
description |
In the CNS, the chemokine CX3CL1 (fractalkine) is expressed on neurons while its specific receptor CX3CR1 is expressed on microglia and macrophages. Microglia play an important role in health and disease through CX3CL1/CX3CR1 signaling, and in many neurodegenerative disorders, microglia dysregulation has been associated with neuro-inflammation. We have previously shown that CX3CL1 has neuroprotective effects against cerebral ischemia injury. Here, we investigated the involvement of CX3CL1 in the modulation of microglia phenotype and the underlying neuroprotective effect on ischemia injury. The expression profiles of anti- and pro-inflammatory genes showed that CX3CL1 markedly inhibited microglial activation both in vitro and in vivo after permanent middle cerebral artery occlusion (pMCAO), accompanied by an increase in the expression of anti-inflammatory genes. Moreover, CX3CL1 induces a metabolic switch in microglial cells with an increase in the expression of genes related to the oxidative pathway and a reduction in those related to the glycolytic pathway, which is the metabolic state associated to the pro-inflammatory phenotype for energy production. The data reported in this paper suggest that CX3CL1 protects against cerebral ischemia modulating the activation state of microglia and its metabolism in order to restrain inflammation and organize a neuroprotective response against the ischemic insult. |
topic |
CX3CL1 microglia ischemia neuroprotection neuroinflammation |
url |
https://www.frontiersin.org/article/10.3389/fncel.2019.00414/full |
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