The role of excitatory amino acid transporters in neuroprotection and neuropathology

Glutamate is the most abundant excitatory amino acid found within the CNS. This neurotransmitter has been shown to play a prominent role in development, plasticity, learning and memory. Sodium dependent glutamate transporters (EAAT1-5) facilitate termination of glutamate signaling. Excitatory amino acid transporter 2 (EAAT2) is responsible for up to 90% of all glutamate uptake and is primarily localized on astrocytes. Multiple disease states have been associated with alterations in EAAT2 expression level and function. Many studies have attempted to elevate EAAT2 expression to compensate for loss of function and expression in disease. Elevated EAAT2 expression has been noted during ischemic preconditioning (IPC) but is just one of many components altered under IPC. The aim of this study was to isolate and characterize the contribution of increased astrocytic EAAT2 expression towards neuroprotection. A novel recombinant adeno-associated virus, rAAV1-GFAP-EAAT2, was designed and used to selectively increase astrocytic EAAT2 expression. Under conditions of oxygen glucose deprivation, elevated astrocytic EAAT2 expression was shown to offer neuroprotection. This approach offers the first evidence supporting sole regulation of EAAT2 expression in astrocytes and the specific role of this transporter in neuroprotection. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.