Regulation of Glutamate Transport in Developing Rat Oligodendrocytes

Abstract

Glutamate released from synaptic vesicles mediates excitatory neurotransmission by stimulating glutamate receptors. Glutamate transporters maintain low synaptic glutamate levels critical for this process, a role primarily attributed to astrocytes. Recently, vesicular release of glutamate from unmyelinated axons in the rat corpus callosum has been shown to elicit AMPA receptor-mediated currents in glial progenitor cells. Glutamate transporters are the only mechanism of glutamate clearance, yet very little is known about the role of glutamate transporters in normal development of oligodendrocytes (OLs) or in excitotoxic injury to OLs. We found that OLs in culture are capable of sodium-dependent glutamate uptake with a K m of 10 Ϯ 2 M and a V max of 2.6, 5.0, and 3.8 nmol ⅐ min Ϫ1 ⅐ mg Ϫ1 for preoligodendrocytes, immature, and mature OLs, respectively. Surprisingly, EAAC1, thought to be exclusively a neuronal transporter, contributes more to [ 3 H]L-glutamate uptake in OLs than GLT1 or GLAST. These data suggest that glutamate transporters on oligodendrocytes may serve a critical role in maintaining glutamate homeostasis at a time when unmyelinated callosal axons are engaging in glutamatergic signaling with glial progenitors. Furthermore, GLT1 was significantly increased in cultured mature OLs contrary to in vivo data in which we have shown that, although GLT1 is present on developing OLs when unmyelinated axons are prevalent in the developing rat corpus callosum, after myelination, GLT1 is not expressed on mature OLs. The absence of GLT1 in mature OLs in the rat corpus callosum and its presence in mature rat cultured OLs may indicate that a signaling process in vivo is not activated in vitro.

The Fate of Synaptic Input to NG2 Glial Cells: Neurons Specifically Downregulate Transmitter Release onto Differentiating Oligodendroglial Cells

“…3). This is in good agreement with a previous study using a similar photolytic technique on oligodendrocytes (Regan et al, 2007) and with previous reports investigating the expression of glutamate transporter proteins and glutamate uptake rates in oligodendrocytes (Arranz et al, 2008;DeSilva et al, 2009). Interestingly, our experiments with synaptic stimulation (Fig.…”

Development of a simple in vitro mature mixed glial model to investigate differential expression of cell markers on glial cells and their potential as targets in multiple sclerosis

“…In addition to EAAT1/GLAST, EAAT2/GLT-1 is also abundantly expressed on astrocytes in the CNS. GLT-1 has also been reported in a small number of studies to be present on oligodendrocytes (DeSilva et al, 2009;Domercq et al, 2005;Werner et al, 2001). This will also be assessed in the current chapter.…”

“…GLT-1 also has several known isoforms, which have been found to be differentially distributed at the regional, cellular and subcellular level in astrocytes in the hippocampus, lateral septum, cerebral cortex and striatum, in neurons, in photoreceptors of the retina, and in the liver (Patel and Klein, 2011;Jitoku et al, 2011;Magnotti et al, 2011;Lehre et al, 1995;Schmitt et al, 2002;Schreiner et al, 2014;Rauen et al, 2004). Several studies have reported GLT-1 expression by mature oligodendrocytes (DeSilva et al, 2009;Domercq et al, 2005;Werner et al, 2001), although that has been disputed by other investigators, who have reported that GLT-1 expression is lost in mature oligodendrocytes. One study found that mature oligodendrocytes in culture, but not in brain tissue, expressed GLT-1, and suggested that an in vivo signaling mechanism controlling loss of GLT-1 was absent in vitro (DeSilva et al, 2009).…”

“…The EAATs are differentially expressed, with GLAST and GLT-1 being the EAATs most abundant on astrocytes in the rodent brain (Domercq et al, 1999;DeSilva et al, 2009). There are variable reports of GLAST expression on oligodendrocytes.…”

“…There are variable reports of GLAST expression on oligodendrocytes. Some early studies state that GLAST is expressed by oligodendrocytes (Kondo et al, 1995;Domercq et al, 1999), but others have not been able to replicate this (Lehre et al, 1995, Schmitt et al, 1997, Cahoy et al, 2008, Jungblut et al, 2012, Zhou and Danbolt, 2013, or have found that GLAST is only transiently expressed on immature oligodendrocytes (DeSilva et al, 2009) or only on subgroups of oligodendrocytes in specific brain regions (van Landeghem et al, 2007). It has recently been speculated that oligodendrocytes probably do not express GLAST, but that the literature regarding GLAST expression has become confusing, largely due to poorly controlled immunocytochemistry (Zhou and Danbolt, 2013).…”