Expression of the glutamate transporters in human temporal lobe epilepsy

Glutamate is the major excitatory neurotransmitter in the central nervous s ystem and is implicated in the pathogenesis of neurodegenerative diseases. Five human glutamate transporters have been cloned and are responsible for the removal of potentially excitotoxic excess glutamate from the extracellu lar space. In this study we consider whether there are selective changes in the expression of the glutamate transporters in the medial temporal cortex and hippocampus from temporal lobe epilepsy patients, which might contribu te to the development or maintenance of seizures. Since disruption of the g lial transporter excitatory amino acid transporter 2 in mice results in let hal spontaneous seizures, we were interested primarily in studying changes in this transporter Using in situ hybridization we show that there was no r eduction in the level of excitatory amino acid transporter 2 encoding messe nger RNA in the temporal lobe epilepsy cases compared to post mortem contro ls and indeed there was a relative increase in content of excitatory amino acid transporter 2 messenger RNA per cell in temporal lobe epilepsy cases. Western blotting showed that there was no change in the excitatory amino ac id transporter 2 protein content in temporal lobe epilepsy cases as compare d to post mortem controls. A small reduction in the level of the second ast roglial transporter protein, excitatory amino acid transporter 1, was obser ved in temporal lobe epilepsy cases. Surprisingly, immunohistochemical expe riments using a polyclonal anti-excitatory amino acid transporter 2 antibod y, showed a different localization of this protein in epilepsy derived tiss ue as compared to post mortem controls although glial markers such as glial fibrillary acidic protein and glutamine synthase showed similar patterns o f staining. However, repeating this experiment using control tissue from no n-temporal lobe epilepsy biopsies demonstrated that this change in the exci tatory amino acid transporter 2 transporter localization occurred post mort em. These data suggest that major changes in the level of expression of the glu tamate transporters do not play an important role in the development of hum an temporal lobe epilepsy but may be implicated the aetiology of other type s of epilepsy. (C) 1998 IBRO. Published by Elsevier Science Ltd.