CXCR3-Dependent Microglial Recruitment Is Essential for Dendrite Loss after Brain Lesion

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.

Identification of Chemoattractive Factors Involved in the Migration of Bone Marrow-Derived Mesenchymal Stem Cells to Brain Lesions Caused by Prions

“…2). The involvement of CXCL12/ CXCR4 signaling in hMSCs migration is consistent with findings in hypoglossal nerve injury (24), ischemic (63), and glioma (11) (6,45). In prion diseases, impairment of microglial migration, associated with the increased accumulation of PrP Sc but prolongation of survival, has been reported in CXCR3 gene deficient mice infected with prions (47).…”

Facial nerve injuries cause changes in central nervous system microglial cells

“…Estas modificaciones también podrían relacionarse con la presencia de microglías activadas muy tempranamente en la corteza motora tras la lesión. De hecho, se sabe que es necesario el reclutamiento y la proliferación de las microglías para que se produzcan alteraciones dendríticas neuronales después de una lesión (24).…”

“…Por otra parte, se sabe que, tras lesiones del sistema nervioso central, el árbol dendítrico de las neuronas sometidas a axotomía y de las 'denervadas' se remodela y se registra un aumento en la expresión de las quimiocinas, las cuales activan las células de la microglía residentes; se ha planteado que dicha activación es necesaria para que ocurra la remodelación neuronal después de una lesión (24,25). Es por esto que las células de la microglía se consideran los sensores más sensibles de alteraciones en el sistema nervioso central.…”

Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE

“…CLN were isolated 24 h (n=5) and 72 h (n=5) after MCAO. Entorhinal cortex lesion (ECL) and facial nerve axotomy (FNA) were performed as described [32] in C57BL/6 mice (n=5 and n=3, respectively; Charles River). CLN were isolated 7 days later.…”