Abstract
Multiple sclerosis (MS) is an autoimmune disease causing central nervous system (CNS) demyelination and axonal injury. In the last years the importance of astrocytes in MS is rapidly increasing, recognizing astrocytes as highly active players in MS pathogenesis. Usually the role assigned to astrocytes in MS lesions has been the formation of the glial scar, but now their implication during lesion formation and the immune response increasingly recognized. Since astrocytes are a heterogeneous cell population with diverse roles in the CNS, the aim of this study was to analyze the putative clonal response of astrocytes in a demyelinating scenario. To undertake this aim, we used the induced experimental autoimmune encephalomyelitis (EAE) as a murine model for MS in previously electroporated mice with in vivo multicolor lineage tracing system, the StarTrack methodology. Our data revealed a variety of morphological changes that were different among distinct clones. In many cases, cells of the same clone responded equally to the injury, while in other cases clonally-related cells responded differently to the injury. Therefore, whereas some clones exhibited a strong morphological alteration, other clones located at similar distances to the lesion were apparently unresponsive. Thus, at present there is no compelling evidences that clonal relationship influences the position or function of astrocytes in the EAE model. Further, the coexistence of different astroglial clonal responses to the bran injury reveals the significance of development to determine the astrocyte features that respond to brain injuries.
Highlights
Multiple sclerosis (MS) is a chronic, disabling autoimmune and neurological disorder targeting the white and gray matter of the central nervous system (CNS; Lassmann, 2012; Prins et al, 2015; van Munster et al, 2015)
Taking advantage of this technology, we analyzed the morphological response of clonally-related astrocytes to demyelinating lesions in murine myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model that resembles immunopathological and neurobiological aspects of MS
In the EAE MOG-induced model the main affectation is located in the spinal cord, EAE experiments in mice demonstrated that, as occurs in human MS, the cerebral cortex is affected (Procaccini et al, 2015)
Summary
Multiple sclerosis (MS) is a chronic, disabling autoimmune and neurological disorder targeting the white and gray matter of the central nervous system (CNS; Lassmann, 2012; Prins et al, 2015; van Munster et al, 2015). Star Track provided in vivo evidence of the relationship between heterogeneity and lineage in astrocytes (García-Marqués and López-Mascaraque, 2013) as well as how groups of astrocyte clones respond differentially to cortical injury (Martín-López et al, 2013). Taking advantage of this technology, we analyzed the morphological response of clonally-related astrocytes to demyelinating lesions in murine myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model that resembles immunopathological and neurobiological aspects of MS. Our data show that most astrocytes are distributed whether or not they share a clonal relationship, while a large diversity of morphological changes were different among different clones
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