Endothelin-B Receptor Activation in Astrocytes Regulates the Rate of Oligodendrocyte Regeneration during Remyelination

Hammond, Timothy R.; McEllin, Brian; Morton, Paul D.; Raymond, Matthew; Dupree, Jeff; Gallo, Vittorio

doi:10.1016/j.celrep.2015.11.002

Cited by 49 publications

(46 citation statements)

References 34 publications

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“…The same authors also reported high levels of immunoreactive ET-1 in spinal cord-localized inflammatory and neuroglial cells [31]. These observations are of relevance considering that Hammond et al (2014) have recently shown that ET-1 is a negative regulator of oligodendrocyte progenitor cell-dependent repair of demyelinated lesions [32]. In support of the latter observation, myelin contents were, in the present study, found to be higher in naive and even one week after EAE immunized mMCP-4 KO mice than in their WT congeners.…”

Section: Discussionmentioning

confidence: 87%

Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis

Desbiens

Lapointe

Gharagozloo

et al. 2016

Mediators of Inflammation

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Experimental autoimmune encephalomyelitis (EAE) is a mouse model that reproduces cardinal signs of clinical, histopathological, and immunological features found in Multiple Sclerosis (MS). Mast cells are suggested to be involved in the main inflammatory phases occurring during EAE development, possibly by secreting several autacoids and proteases. Among the latter, the chymase mouse mast cell protease 4 (mMCP-4) can contribute to the inflammatory response by producing endothelin-1 (ET-1). The aim of this study was to determine the impact of mMCP-4 on acute inflammatory stages in EAE. C57BL/6 wild type (WT) or mMCP-4 knockout (KO) mice were immunized with MOG35–55 plus complete Freund's adjuvant followed by pertussis toxin. Immunized WT mice presented an initial acute phase characterized by progressive increases in clinical score, which were significantly reduced in mMCP-4 KO mice. In addition, higher levels of spinal myelin were found in mMCP-4 KO as compared with WT mice. Finally, whereas EAE triggered significant increases in brain levels of mMCP-4 mRNA and immunoreactive ET-1 in WT mice, the latter peptide was reduced to basal levels in mMCP-4 KO congeners. Together, the present study supports a role for mMCP-4 in the early inflammatory phases of the disease in a mouse model of MS.

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Section: Discussionmentioning

confidence: 87%

Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis

Desbiens

Lapointe

Gharagozloo

et al. 2016

Mediators of Inflammation

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“…Our laboratory recently characterized a protein secreted by reactive astrocytes, endothelin-1 (ET-1), as a negative regulator of NG2 glial differentiation and functional remyelination 56,57 . Blocking ET-1 signaling by either pharmacological or genetic approaches enhances maturation of NG2 glia into oligodendrocytes after focal demyelination of the corpus callosum.…”

Section: Is the Glial Scar Inhibitory Or Beneficial To Regeneration?mentioning

confidence: 99%

The diversity and disparity of the glial scar

2017

Self Cite

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Injury or disease to the CNS results in multifaceted cellular and molecular responses. One such response, the glial scar, is a structural formation of reactive glia around an area of severe tissue damage. While traditionally viewed as a barrier to axon regeneration, beneficial functions of the glial scar have also been recently identified. In this Perspective, we discuss the divergent roles of the glial scar during CNS regeneration and explore the possibility that these disparities are due to functional heterogeneity within the cells of the glial scar—specifically, astrocytes, NG2 glia and microglia.

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“…In addition to these OPC-directed drugs, several experimental compounds have been described to trigger signaling pathways modulating oligodendrogenesis. The endothelin (ET) receptor antagonist BQ788 was demonstrated to block endothelin-B receptor activation on astrocytes, thereby rescuing oligodendrogenesis and promoting remyelination [133]. The flavonoid molecule quercetin leads to enhanced oligodendrogenesis and remyelination in several ways, as it suppresses Notch signaling by inhibiting γ-secretase activity and disrupts the binding of β-catenin to TCF4 [134].…”

Section: Regulators Of Glia Cell Fate: Avenues To Adjust Aberrant Whimentioning

confidence: 99%

Aberrant Oligodendrogenesis in Down Syndrome: Shift in Gliogenesis?

Reiche

Küry

Göttle

2019

Cells

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Down syndrome (DS), or trisomy 21, is the most prevalent chromosomal anomaly accounting for cognitive impairment and intellectual disability (ID). Neuropathological changes of DS brains are characterized by a reduction in the number of neurons and oligodendrocytes, accompanied by hypomyelination and astrogliosis. Recent studies mainly focused on neuronal development in DS, but underestimated the role of glial cells as pathogenic players. Aberrant or impaired differentiation within the oligodendroglial lineage and altered white matter functionality are thought to contribute to central nervous system (CNS) malformations. Given that white matter, comprised of oligodendrocytes and their myelin sheaths, is vital for higher brain function, gathering knowledge about pathways and modulators challenging oligodendrogenesis and cell lineages within DS is essential. This review article discusses to what degree DS-related effects on oligodendroglial cells have been described and presents collected evidence regarding induced cell-fate switches, thereby resulting in an enhanced generation of astrocytes. Moreover, alterations in white matter formation observed in mouse and human post-mortem brains are described. Finally, the rationale for a better understanding of pathways and modulators responsible for the glial cell imbalance as a possible source for future therapeutic interventions is given based on current experience on pro-oligodendroglial treatment approaches developed for demyelinating diseases, such as multiple sclerosis.

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Endothelin-B Receptor Activation in Astrocytes Regulates the Rate of Oligodendrocyte Regeneration during Remyelination

Cited by 49 publications

References 34 publications

Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis

Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis

The diversity and disparity of the glial scar

Aberrant Oligodendrogenesis in Down Syndrome: Shift in Gliogenesis?

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