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Intravital Imaging of Axonal Interactions with Microglia and Macrophages in a Mouse Dorsal Column Crush Injury
Published on: November 23, 2014
CXCR3-dependent microglial recruitment is essential for dendrite loss after brain lesion
Angelika Rappert1, Ingo Bechmann, Tatyana Pivneva
1Department of Cellular Neuroscience, Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany.
Abstract:
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.
Insights
CXCR3 signaling is crucial for microglia recruitment to brain injury sites, impacting neuronal reorganization. Blocking this pathway preserves denervated dendrites, highlighting its role in CNS repair.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key immune cells in the central nervous system (CNS), responding to brain pathology by migrating to injury sites.
- The chemokine CXCL10 and its receptor CXCR3 are implicated in microglial activation and migration.
- CXCR3 signaling's role in microglial responses to CNS injury requires further elucidation.
Purpose of the Study:
- To investigate the impact of CXCR3 signaling on microglial cellular responses following entorhinal cortex lesion.
- To determine if CXCR3 signaling is essential for microglial recruitment and subsequent neuronal reorganization after CNS injury.
Main Methods:
- Utilized a mouse model with entorhinal cortex lesion to study microglial responses.
- Compared wild-type mice with CXCR3 knock-out mice to assess the role of the CXCR3 receptor.
- Analyzed microglial migration, dendritic integrity, and proliferation using facial nerve axotomy as a control.
Main Results:
- Microglia successfully migrated to the lesion site in wild-type mice, leading to denervated dendrite loss.
- Impaired microglial recruitment was observed in CXCR3 knock-out mice.
- Denervated distal dendrites were preserved in CXCR3 knock-out mice at the lesion site.
- No differences in microglial proliferation were found between genotypes after facial nerve axotomy.
Conclusions:
- CXCR3 signaling is critical for microglia recruitment to sites of CNS injury, but not for their proliferation.
- Microglial recruitment mediated by CXCR3 is essential for neuronal reorganization and subsequent dendrite loss after entorhinal cortex lesion.
