AMPA glutamate receptor-mediated calcium signaling is transiently enhanced during development of oligodendrocytes

Abstract

-permeable, AMPA-GluR explains the selective susceptibility to excitotoxicity of cells at these stages of oligodendroglial differentiation, and is likely to be important to these cells in the trans-synaptic Ca 2+ -signaling from glutamatergic neurons, which occurs in hippocampus in vivo.

Functional glutamate transport in rodent optic nerve axons and glia

“…Expression of AMPA/kainate receptors is particularly marked in immature cells of the oligodendrocyte lineage (Itoh et al, 2002), which in the neonatal optic nerve are in the process of forming an exquisitely close morphological arrangement with neighbouring axons (Butt and Ransom, 1993). We and others have recently demonstrated the presence of functional NMDA-type glutamate receptors in oligodendrocyte processes (Salter and Fern, 2005;Káradóttir et al, 2005;Micu et al, 2006)).…”

NF‐Y‐dependent regulation of glutamate receptor 4 expression and cell survival in cells of the oligodendrocyte lineage

“…Here, exposure to hypoxia that induces strong elevations in the concentration of extracellular glutamate is associated with a significant increase in GluA4 immunoreactivity within immature oligodendroglia. The expression of Gria4 is regulated developmentally (Itoh et al, 2002; Hossain et al, 2014), thus the direction of excitotoxicity‐induced regulation of Gria4 in oligodendroglia may depend on maturational status. Indeed, Oli‐neu cells cultured under the conditions used in the present study exhibit low levels of immunoreactivity to anti‐O4 (Toutouna et al, 2016), suggesting that this cell line holds a more immature position in the lineage than pOPC, which typically exhibit strong anti‐04 staining.…”

“…These observations suggest that a substantial number of OPC AMPAR lack GluA2 subunits since inclusion of this subunit limits the permeability of AMPAR to Ca 2+ (Geiger et al, 1995; Hollmann, Hartley, & Heinemann, 1991). In support of this, cultured OPC express high levels of GluA3 and 4 (Hossain et al, 2014; Itoh et al, 2002) which may assemble to form Ca 2+ permeable AMPAR, and GluA4 is the predominant subunit expressed by OPC in the developing white matter of rodents and humans (Talos, Fishman, et al, 2006; Talos, Follett, et al, 2006). Importantly, the timing of GluA4 expression in these systems corresponds with an established window of vulnerability during which OPC are selectively injured by hypoxic‐ischemic conditions (Back et al, 2002; Back et al, 2001; reviewed in Fern, Matute, & Stys, 2014), and GluA4 is highly expressed in neural cells vulnerable to excitotoxic cell death (Page & Everitt, 1995).…”

“…OPC express all four subunits, although GluA1 represents a minor contributor compared with GluA2–4 in vitro (Hossain, Liu, Fragoso, & Almazan, 2014; Itoh et al, 2002), and appears to be entirely absent from OPC in vivo (Kougioumtzidou et al, 2017). Activation of OPC AMPAR provokes an influx of Ca 2+ (Ge et al, 2006; Haberlandt et al, 2011; Hamilton, Vayro, Wigley, & Butt, 2010; Itoh et al, 2002) that can mediate excitotoxic injury in vitro (Alberdi, Sanchez‐Gomez, Marino, & Matute, 2002; Deng, Rosenberg, Volpe, & Jensen, 2003; Li & Stys, 2000; Sanchez‐Gomez & Matute, 1999). These observations suggest that a substantial number of OPC AMPAR lack GluA2 subunits since inclusion of this subunit limits the permeability of AMPAR to Ca 2+ (Geiger et al, 1995; Hollmann, Hartley, & Heinemann, 1991).…”

Brain Injury in Preterm Infants

“…Glutamate is produced by the developing oligodendrocytes and axons (Rossi, Oshima et al 2000;Desilva, Kinney et al 2007) and is highly toxic in vitro (Choi 1992). Moreover, it renders even more vulnerable the premyelinating oligodendrocytes, though not the mature cells (Itoh, Beesley et al 2002).…”