Article

NMDA receptor signaling in oligodendrocyte progenitors is not required for oligodendrogenesis and myelination.

The Solomon H. Snyder Department of Neuroscience and Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21205, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 08/2011; 31(35):12650-62. DOI: 10.1523/JNEUROSCI.2455-11.2011
Source: PubMed

ABSTRACT Oligodendrocyte precursor cells (OPCs) express NMDA receptors (NMDARs) and form synapses with glutamatergic neurons throughout the CNS. Although glutamate influences the proliferation and maturation of these progenitors in vitro, the role of NMDAR signaling in oligodendrogenesis and myelination in vivo is not known. Here, we investigated the consequences of genetically deleting the obligatory NMDAR subunit NR1 from OPCs and their oligodendrocyte progeny in the CNS of developing and mature mice. NMDAR-deficient OPCs proliferated normally, achieved appropriate densities in gray and white matter, and differentiated to form major white matter tracts without delay. OPCs also retained their characteristic physiological and morphological properties in the absence of NMDAR signaling and were able to form synapses with glutamatergic axons. However, expression of calcium-permeable AMPA receptors (AMPARs) was enhanced in NMDAR-deficient OPCs. These results suggest that NMDAR signaling is not used to control OPC development but to regulate AMPAR-dependent signaling with surrounding axons, pointing to additional functions for these ubiquitous glial cells.

0 Followers
 · 
126 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: NG2 cells (polydendrocytes) are the fourth major non-neuronal cell type in the central nervous system parenchyma. They exhibit diverse properties, ranging from their well-established role as oligodendrocyte precursors to their ability to respond to neurotransmitters released by synaptic and non-synaptic mechanisms. The functional diversity of NG2 cells has prompted the question of whether they represent a single cellular entity or multiple distinct cell populations. This review first summarizes recent findings on the nature and mechanism underlying the diversity of NG2 cells with regard to their proliferative and differentiation behavior. This will be followed by a synopsis of observations on how their microenvironment, particularly neuronal activity, influences their dynamic behavior, and how these changes in NG2 cells could in turn influence neural function and animal behavior. GLIA 2014
    Glia 08/2014; 62(8). DOI:10.1002/glia.22664 · 6.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Multipotent cells from the juvenile subventricular zone (SVZ) possess the ability to differentiate into new neural cells. Depending on local signals, SVZ can generate new neurons, astrocytes, or oligodendrocytes. We previously demonstrated that activation of NMDA receptors in SVZ progenitors increases the rate of oligodendrocyte differentiation. Here we investigated the mechanisms involved in NMDA receptor-dependent differentiation. Using functional studies performed with the reporter gene luciferase we found that activation of NMDA receptor stimulates PKC. In turn, stimulation of PKC precedes the activation of NADPH oxidase (NOX) as demonstrated by translocation of the p67phox subunit to the cellular membrane. We propose that NOX2 is involved in the transduction of the signal from NMDA receptors through PKC activation as the inhibitor gp91 reduced their pro-differentiation effect. In addition, our data and that from other groups suggest that signaling through the NMDA receptor/PKC/NOX2 cascade generates ROS that activate the PI3/mTOR pathway and finally leads to the generation of new oligodendrocytes.
    Frontiers in Cellular Neuroscience 12/2013; 7:261. DOI:10.3389/fncel.2013.00261 · 4.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Glutamate receptors of the N-methyl-D-aspartate (NMDA) type are involved in many cognitive processes, including behavior, learning and synaptic plasticity. For a long time NMDA receptors were thought to be the privileged domain of neurons; however, discoveries of the last 25 years have demonstrated their active role in glial cells as well. Despite the large number of studies in the field, there are many unresolved questions connected with NMDA receptors in glia that are still a matter of debate. The main objective of this review is to shed light on these controversies by summarizing results from all relevant works concerning astrocytes, oligodendrocytes and polydendrocytes (also known as NG2 glial cells) in experimental animals, further extended by studies performed on human glia. The results are divided according to the study approach to enable a better comparison of how findings obtained at the mRNA level correspond with protein expression or functionality. Furthermore, special attention is focused on the NMDA receptor subunits present in the particular glial cell types, which give them special characteristics different from those of neurons - for example, the absence of Mg(2+) block and decreased Ca(2+) permeability. Since glial cells are implicated in important physiological and pathophysiological roles in the central nervous system (CNS), the last part of this review provides an overview of glial NMDA receptors with respect to ischemic brain injury.
    Current Neuropharmacology 05/2013; 11(3):250-62. DOI:10.2174/1570159X11311030002 · 2.35 Impact Factor

Preview

Download
3 Downloads
Available from