CXCR3-Dependent Microglial Recruitment Is Essential for Dendrite Loss after Brain Lesion
Autor: | Hendrikus Boddeke, Adam D. Kovac, Helmut Kettenmann, Knut Biber, Jacqueline Mahlo, Robert Nitsch, Tatyana Pivneva, Angelika Rappert, Ingo Bechmann, Craig Gerard, Christiane Nolte |
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Přispěvatelé: | Molecular Neuroscience and Ageing Research (MOLAR), Translational Immunology Groningen (TRIGR) |
Rok vydání: | 2004 |
Předmět: |
receptor
medicine.medical_treatment REACTIVE ASTROCYTES microglia Cell Count CHEMOKINE RECEPTOR CXCR3 migration CXCR3 Hippocampus facial nerve lesion Mice Cell Movement GFAP MESSENGER-RNA entorhinal cortex lesion RAT FASCIA-DENTATA dendritic loss Mice Knockout Microglia Reverse Transcriptase Polymerase Chain Reaction CXCL10 General Neuroscience Axotomy Immunohistochemistry ALZHEIMERS-DISEASE Facial Nerve medicine.anatomical_structure EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS Receptors Chemokine medicine.symptom Function and Dysfunction of the Nervous System Chemokines CXC Signal Transduction Cellular/Molecular Receptors CXCR3 Perforant Pathway Central nervous system PARVALBUMIN-IMMUNOREACTIVE NEURONS Dendrite Biology Lesion medicine Animals INDUCIBLE PROTEIN-10 ENTORHINAL CORTEX chemokine CENTRAL-NERVOUS-SYSTEM Dendrites Entorhinal cortex Chemokine CXCL10 Mice Inbred C57BL nervous system Astrocytes Brain Injuries Neuroscience |
Zdroj: | The Journal of Neuroscience, 24(39), 8500-8509. Oxford University Press |
ISSN: | 1529-2401 0270-6474 |
DOI: | 10.1523/jneurosci.2451-04.2004 |
Popis: | Microglia are the resident macrophage population of the CNS and are considered its major immunocompetent elements. They are activated by any type of brain pathology and can migrate to the lesion site. The chemokine CXCL10 is expressed in neurons in response to brain injury and is a signaling candidate for activating microglia and directing them to the lesion site. We recently identified CXCR3, the corresponding receptor for CXCL10, in microglia and demonstrated that this receptor system controls microglial migration. We have now tested the impact of CXCR3 signaling on cellular responses after entorhinal cortex lesion. In wild-type mice, microglia migrate within the first 3 d after lesion into the zone of axonal degeneration, where 8 d after lesion denervated dendrites of interneurons are subsequently lost. In contrast, the recruitment of microglia was impaired in CXCR3 knock-out mice, and, strikingly, denervated distal dendrites were maintained in zones of axonal degeneration. No differences between wild-type and knock-out mice were observed after facial nerve axotomy, as a lesion model for assessing microglial proliferation. This shows that CXCR3 signaling is crucial in microglia recruitment but not proliferation, and this recruitment is an essential element for neuronal reorganization. |
Databáze: | OpenAIRE |
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