Adult-born SVZ progenitors receive transient synapses during remyelination in corpus callosum. Nat Neurosci

Center for Neuroscience Research, Children's National Medical Center, Washington, DC, USA.
Nature Neuroscience (Impact Factor: 16.1). 02/2010; 13(3):287-9. DOI: 10.1038/nn.2500
Source: PubMed


We found that demyelinated axons formed functional glutamatergic synapses onto adult-born NG2(+) oligodendrocyte progenitor cells (OPCs) migrating from the subventricular zone after focal demyelination of adult mice corpus callosum. This glutamatergic input was substantially reduced compared with endogenous callosal OPCs 1 week after lesion and was lost on differentiation into oligodendrocytes. Therefore, axon-oligodendrocyte progenitor synapse formation is a transient and regulated step that occurs during remyelination of callosal axons.

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    • "Among the signals that have been proposed as cues for differentiation and myelination are several neurotransmitters and growth factors; they probably act as paracrine or autocrine signals in addition to their role in synaptic transmission, and they have diverse effects either stimulating or regulating specific membrane receptors expressed in the OPC and OLG membrane (Káradóttir and Attwell, 2007; Boulanger and Messier 2014). Thus, adenosine, glutamate, GABA and ATP can modulate proliferation, differentiation, and migration of OPC, as well as OLG survival and myelination (e.g., Gallo et al., 1996; Gudz et al., 2006; Ishibashi et al., 2006; Domercq et al., 2010; Etxeberria et al., 2010; Wake et al., 2011; Zonouzi et al., 2015). In particular, both OPC and mature OLG express the two main subtypes of GABA receptors, GABA A (Hoppe and Kettenmann 1989; Von Blankenfeld et al., 1991; Berger et al., 1992; Cahoy et al., 2008) and GABA B (Luyt et al., 2007). "
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    ABSTRACT: Myelination requires oligodendrocyte-neuron communication, and both neurotransmitters and contact interactions are essential for this process. Oligodendrocytes are endowed with neurotransmitter receptors whose expression levels and properties may change during myelination. However, only scant information is availble about the extent and timing of these changes or how they are regulated by oligodendrocyte-neuron interactions. Here, we used electrophysiology to study the expression of ionotropic GABA (γ-aminobutyric acid), glutamate, and ATP receptors in oligodendrocytes derived from the optic nerve and forebrain cultured either alone or in the presence of dorsal root ganglion neurons. We observed that oligodendrocytes from both regions responded to these transmitters at one day in culture. After the first day in culture, however, GABA sensitivity diminished drastically to less than 10%, while that of glutamate and ATP remained constant. In contrast, the GABA response amplitude was sustained and remained stable in oligodendrocytes co-cultured with dorsal root ganglion neurons. Immunochemistry and pharmacological properties of the responses indicated that they were mediated by distinctive GABAA receptors and that, in co-culture with neurons, the oligodendrocytes bearing the receptors were those in direct contact with axons. These results reveal that GABAA receptor regulation in oligodendrocytes is driven by axonal cues, and that GABA signaling may play a role in myelination and/or during axon-glia recognition.
    Molecular pharmacology 11/2015; DOI:10.1124/mol.115.100594 · 4.13 Impact Factor
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    • "NG2-OPCs function as precursors to oligodendrocytes and closely interact with axons in various brain regions including the corpus callosum, cortex, and hippocampus [further reviewed in section role of NG2-OPCs in addiction; (Kukley et al., 2007; Ziskin et al., 2007; Karadottir et al., 2008; Ge et al., 2009; Etxeberria et al., 2010)]. Electrophysiological studies revealed glutamatergic synapses transmitting AMPA receptor-mediated currents between axons and NG2-OPCs, indicating functional synapses (Ziskin et al., 2007; Etxeberria et al., 2010). Furthermore, it has been demonstrated that the NG2-axon synapses could help to promote growth and myelination after nerve injury (Yang et al., 2006). "

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    • "a fraction of the synaptic cell adhesion molecule SynCAM 1 within a subset of NG2 cells of the early postnatal mouse brain ( Galuska et al . , 2010 ; Rollenhagen et al . , 2012 ) . NG2 cells are able to communicate with neurons via specialized neuron - NG2 cell synapses ( Bergles et al . , 2000 ; Karadottir et al . , 2005 ; Kukley et al . , 2007 ; Etxeberria et al . , 2010 ) . This axo - glial signaling may be involved in the onset of myelination ( De Biase et al . , 2010 ; Kukley et al . , 2010 ) . As SynCAM 1 is critical for assembly , organization and maintenance of neuronal synapses ( Biederer et al . , 2002 ; Stagi et al . , 2010 ; Fogel et al . , 2011 ) it may also contribute to the formation of syn"
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    ABSTRACT: Oligodendrocyte precursor cells (OPCs) are the progenitors of myelinating oligodendrocytes in brain development and repair. Successful myelination depends on the control of adhesiveness during OPC migration and axon contact formation. The decoration of cell surface proteins with the glycan polysialic acid (polySia) is a key regulatory element of OPC interactions during development and under pathological conditions. By far the major protein carrier of polySia is the neural cell adhesion molecule NCAM, but recently, polysialylation of the synaptic cell adhesion molecule SynCAM 1 has been detected in the developing mouse brain. In mice, polySia-SynCAM 1 is associated with cells expressing NG2, a marker of a heterogeneous precursor cell population, which is the primary source for oligodendrocytes in development and myelin repair but can also give rise to astrocytes and possibly neurons. It is not yet clear if polySia-SynCAM 1 is expressed by OPCs and its occurrence in humans is elusive. By generating uniform human embryonic stem cell-derived OPC cultures, we demonstrate that polySia is present on human OPCs but down-regulated during differentiation into myelin basic protein-positive oligodendrocytes. PolySia on NCAM resides on the isoforms NCAM-180 and NCAM-140, and SynCAM 1 is identified as a novel polySia acceptor in human OPCs. Copyright © 2015. Published by Elsevier B.V.
    Stem Cell Research 03/2015; 8(3). DOI:10.1016/j.scr.2015.03.001 · 3.69 Impact Factor
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