Functional glutamate transport in rodent optic nerve axons and glia

Abstract

Glutamate uptake and potential release via Na + -dependent glutamate transporters is crucial to CNS function and to various forms of injury. Evidence for glutamatemediated damage of oligodendroglia somata and processes in white matter suggests that glutamate regulation in white matter is of particular clinical importance. The expression of glutamate transporters was examined in developing mouse and mature mouse and rat white matter using immuno-histochemistry and immuno-electron microscopy. EAAC1 was the major glutamate transporter detected in oligodendroglia cell membranes in both neonatal and mature optic nerve while GLT1 was the most heavily expressed transporter in the membranes of astrocytes. Both EAAC1 and GLAST were also seen in adult astrocytes but there was little membrane expression of either in the neonate. GLAST, EAAC1 and GLT1 were expressed in neonatal axons with significant amount of GLT1 present in the axolemma, while in mature axons EAAC1 was abundant at the node of Ranvier. Functional glutamate transport was probed in developing mouse optic nerve revealing Na + -dependent, TBOA-blockable uptake of D-aspartate in astrocytes, axons and oligodendrocytes. The data show that in addition to oligodendroglia and astrocytes, axons represent a significant potential sink and source for extracellular glutamate in white matter.

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.…”

Chemoarchitecture of glial fibrillary acidic protein (GFAP) and glutamine synthetase in the rat optic nerve: An immunohistochemical study

“…In the thick clusters, astrocytes express the following glutamate transporters on the cell membrane: GLT-1 (glutamate transporter 1), GLAST (glutamate-aspartate transporter), and EAAC1. Oligodendrocytes express a single glutamate transporter on the cell membrane: EAAC1 52) . Oligodendrocytes also moderately express GS, a key enzyme in glutamate metabolism (the present study).…”

Protecting White Matter From Stroke Injury

“…11 It is premature to say, however, that astrocytes are the major provider of that function in WM as oligodendrocytes and nodal membrane of mature axons can also express glutamate transporters. 62,63 Glutamate transporters in WM are necessary to maintain very low basal levels of extracellular glutamate (the range is mid nmol/L to low µmol/L), and transporter blockade is sufficient to induce excitotoxic damage to oligodendrocytes. 64 Under pathological conditions, however, cells may depolarize and accumulate intracellular Na + leading to reversal of Na + -dependent glutamate transport and toxic glutamate release.…”

“…73,74 The loss of transmembrane Na + gradients also causes slowed or reversed Na + -dependent glutamate uptake, and glutamate slowly accumulates in the extracellular space. 11,63,64 High extracellular glutamate activates a complex sequence of pathological events in WM that are reminiscent of GM excitotoxicity, but with at least a notable difference: the activation of NMDA receptors is not toxic in adult WM 11 (see further on). Depolarization leading to Ca 2+ channel activation and ryanodine signaling 75 and glutamate activation of axonal glutamate receptors can cause release of Ca 2+ from intracellular stores in spinal cord axons 58,59 ( Figure 2).…”