Experimental autoimmune encephalomyelitis (EAE) is an animal model that mimics many aspects of multiple sclerosis (MS). In MS the immune system attacks the white matter of the brain and spinal cord, leading to disability and paralysis. Neurons, oligodendrocytes and myelin are lost due to the release of cytotoxic cytokines, autoantibodies and toxic amounts of the excitatory neurotransmitter glut...

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 ...

The SLC1 family of sodium dependent transporters includes the plasma membrane located glutamate and neutral amino acid ASCT1 ASCT2 [3, 52, 39, 40, 9].

Nontransportable blockers of the glutamate transporters are important tools for investigating mechanisms of synaptic transmission. DL-threo-beta-Benzyloxyaspartate (DL-TBOA) is a potent blocker of all subtypes of the excitatory amino acid transporters (EAATs). We characterized novel L-TBOA analogs possessing a substituent on their respective benzene rings. The analogs significantly inhibited la...

Oligodendrocytes, the myelinating cells of CNS axons, are highly vulnerable to excitotoxic signals mediated by glutamate receptors of the AMPA and kainate classes. Receptors in these cells are commonly activated by glutamate that is released from axons and glial cells. In addition, oligodendrocytes contribute to the control of extracellular glutamate levels by means of their own transporters. H...

Astrocytes are key cellular elements in both the tripartite synapse and the neurovascular unit. To fulfill this dual role in synaptic activity and metabolism, they express a panel of receptors and transporters that sense glutamate. Among them, the GLT-1 and GLAST transporters are known to regulate extracellular glutamate concentrations at excitatory synapses and consequently modulate glutamate ...

DL-threo-b-Benzyloxyaspartate (DL-TBOA), a novel derivative of DL-threo-b-hydroxyaspartate, was synthesized and examined as an inhibitor of sodium-dependent glutamate/aspartate (excitatory amino acid) transporters. DL-TBOA inhibited the uptake of [C]glutamate in COS-1 cells expressing the human excitatory amino acid transporter-1 (EAAT1) (Ki 5 42 mM) with almost the same potency as DL-threo-b-h...

Glutamatergic transmission at mossy fiber (MF) synapses on CA3 pyramidal neurons in the hippocampus is mediated by AMPA, kainate, and NMDA receptors and undergoes presynaptic modulation by metabotropic glutamate receptors. The recruitment of different receptors has thus far been studied by altering presynaptic stimulation to modulate glutamate release and interfering pharmacologically with rece...