Abstract
Myelination is an essential process that consists of the ensheathment of axons by myelin. In the central nervous system (CNS), myelin is synthesized by oligodendrocytes. The proliferation, migration, and differentiation of oligodendrocyte precursor cells constitute a prerequisite before mature oligodendrocytes extend their processes around the axons and progressively generate a multilamellar lipidic sheath. Although myelination is predominately driven by oligodendrocytes, the other glial cells including astrocytes and microglia, also contribute to this process. The present review is an update of the most recent emerging mechanisms involving astrocyte and microglia in myelin production. The contribution of these cells will be first described during developmental myelination that occurs in the early postnatal period and is critical for the proper development of cognition and behavior. Then, we will report the novel findings regarding the beneficial or deleterious effects of astroglia and microglia, which respectively promote or impair the endogenous capacity of oligodendrocyte progenitor cells (OPCs) to induce spontaneous remyelination after myelin loss. Acute delineation of astrocyte and microglia activities and cross-talk should uncover the way towards novel therapeutic perspectives aimed at recovering proper myelination during development or at breaking down the barriers impeding the regeneration of the damaged myelin that occurs in CNS demyelinating diseases.
Highlights
Specialty section: This article was submitted to Non-Neuronal Cells, a section of the journal Frontiers in Cellular Neuroscience
Acute delineation of astrocyte and microglia activities and cross-talk should uncover the way towards novel therapeutic perspectives aimed at recovering proper myelination during development or at breaking down the barriers impeding the regeneration of the damaged myelin that occurs in central nervous system (CNS) demyelinating diseases
Thousands of publications were dedicated to this process notably in the aim to investigate how new oligodendrocyte progenitor cells (OPCs) are recruited to the demyelinating area and differentiate into myelinating oligodendrocytes (Gallo and Armstrong, 2008; Clemente et al, 2013; Domingues et al, 2016; Lloyd et al, 2017)
Summary
Consistent with the above findings, the requirement of astrocyte integrity for the normal development of oligodendrocytes was shown by the analysis of transgenic mouse strains devoid of GFAP expression. GFAP knockout mice exhibit abnormal myelination including the presence of actively myelinating oligodendrocytes in adults, nonmyelinated axons in the optic nerve, reduced myelin thickness in spinal cord and ultrastructural defects such as loosening of myelin sheaths (Liedtke et al, 1996). Physical interactions between oligodendrocytes and astrocytes appear to be required for myelination as shown by analysis of the role of connexins (Cx) 30 and Cx43 present on astrocytes and forming gap junctions with Cx32 and Cx47 present on oligodendrocytes. A mechanism possibly involved is proposed to be disruption of the metabolic support provided by astrocytes to oligodendrocytes in agreement with the gap junction-mediated unidirectional flux that transports the molecules preferentially from astrocytes to oligodendrocytes (Robinson et al, 1993)
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