| Research Abstract |
The amino acids, L-glutamate and GABA serve as major excitatory and inhibitory neurotransmitters, respectively, in the manmmalian brain. High-affinity trantsporters for these amino acids in neurons and glial cells are essential for the removal of these transmitters from the synaptic cleft and for regulating their extracellular concentration. There is compelling evidence that epilepsy is associated with changes in the balance of glutamatergic and GAB Aergic neurotransmission. More recently, it has been suggested that changes in GABA and glutamate transporters may be important in epileptogenesis and seizure propagation. In this article, we focus on the involvement of glutamate transporters in epilepsy. Homozygous mice deficient in, a widely distributed astrocytic glutamate transporter, show lethal spontaneous seizures with behavioral patterns similar to those of NMDA-induced seizures characterized by explosive running followed by maintained opisthotonus and straub tail and increased susceptibility to PTZ-induced seizures. Although spontaneous seizures were not observed in GLAST-, EAAC1-, and EAAT4-deficient mice, GLAST-deficient mice showed the prolongation of the generalized seizure duration of amygdala-kindled seizures and increased susceptibility to PTZ-induced seizures. These results demonstrated that glial glutamate transporters contribute much more than neuronal glutamate transporters to epileptogenesis and seizure propagation. The glial glutamate transporters might be a new target for manipulating epilepsy.
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