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
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