Changes in expression of neuronal and glial glutamate transporters in rat hippocampus following kainate-induced seizure activity

The expression of excitatory amino acid transporters (EAATs) in rat hippoca mpus was studied following kainic acid-induced seizure activity in vivo and in hippocampal slice cultures. Protein and mRNA levels of the glial (EAAT2 ) and neuronal (EAAT3) transporters were determined with affinity-purified antibodies and oligonucleotide probes, respectively. Kainate treatment decr eased EAAT3 immunoreactivity in stratum lacunosum moleculare within 4 h of seizure onset. Upon pyramidal cell death (5 days after kainate treatment), EAAT3 immunoreactivity in stratum pyramidale of CAI and in stratum lacunosu m moleculare was almost completely eliminated. The rapid effect of kainate on EAAT3 expression was confirmed by in situ hybridization; EAAT3 mRNA leve ls were decreased in CA1 and CA3 regions within 4-8 h of seizure onset. Kai nate treatment had an opposite effect on levels and expression of EAAT2. De velopmental studies indicated that the rapid regulation of transporter expr ession was not observed in rats younger than 21 days, an observation congru ent with previous reports regarding the resistance of young rats to kainate . In hippocampal organotypic cultures, which lack a major excitatory input from the entorhinal cortex, kainate produced a slow decrease in [H-3]D-aspa rtate uptake. This study indicates that an early effect of kainate treatmen t consists of down-regulation of the neuronal transporter EAAT3 in restrict ed hippocampal regions, together with a modest increase in the expression o f the glial transporter EAAT2. Differential regulation of neuronal and glia l glutamate transporters may thus play a role in kainate-induced seizure, n eurotoxicity and neuronal plasticity. (C) 1999 Elsevier Science B.V. All ri ghts reserved.