Abstract
Recent findings suggest that synaptic-type glutamate signaling operates between axons and their supporting glial cells. Glutamate reuptake will be a necessary component of such a system. Evidence for glutamate-mediated damage of oligodendroglia somata and processes in white matter suggests that glutamate regulation in white matter structures is also of clinical importance. The expression of glutamate transporters was examined in postnatal Day 14-17 (P14-17) mouse and in mature mouse and rat optic nerve using immuno-histochemistry and immuno-electron microscopy. EAAC1 was the major glutamate transporter detected in oligodendroglia cell membranes in both developing and mature optic nerve, while GLT-1 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 at P14-17. GLAST, EAAC1, and GLT-1 were expressed in P14-17 axons with marked GLT-1 expression in the axolemma, while in mature axons EAAC1 was abundant at the node of Ranvier. Functional glutamate transport was probed in P14-17 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 potential source for extracellular glutamate in white matter during ischaemic conditions, and have the capacity for Na(+)-dependent glutamate uptake. The findings support the possibility of functional synaptic-type glutamate release from central axons, an event that will require axonal glutamate reuptake.
Highlights
Glutamate is the major excitatory neurotransmitter in the mammalian CNS but is neurotoxic and has been implicated in important neurological diseases
We have shown a high capacity for Na-dependent, TBOA-blockable, D-aspartate uptake into central white matter astrocytes, axons and oligodendrocytes in two rodent species at two developmental points
All three of these cellular compartments contain cytoplasmic glutamate. These findings indicating that glutamate regulation is important in white matter and that it is achieved by glutamate transporter expression in axons and oligodendroglia in addition to astrocytes
Summary
Glutamate is the major excitatory neurotransmitter in the mammalian CNS but is neurotoxic and has been implicated in important neurological diseases. High-affinity, Na+-dependent glutamate transporters are responsible for clearing synaptically released glutamate from the extracellular space of the CNS (Gegelashvili and Schousboe, 1998; Anderson and Swanson, 2000; Danbolt, 2001). The voltage and Na+-dependence of these glutamate transporters can result in the reversal of transport under ischemic conditions, which can act as one source of the extracellular glutamate that is responsible for excitotoxic cell injury during disorders such as stroke (Attwell et al, 1993; Anderson and Swanson, 2000). Oligodendrocyte damage is central to loss of function in ischemic white matter injury and is thought to result from glutamate-mediated excitotoxicity (Pantoni et al, 1996; Tekkok and Goldberg, 2001; Dewar et al, 2003)
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