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 hippocampus 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 decreased 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 CA1 and in stratum lacunosum moleculare was almost completely eliminated. The rapid effect of kainate on EAAT3 expression was confirmed by in situ hybridization; EAAT3 mRNA levels were decreased in CA1 and CA3 regions within 4-8 h of seizure onset. Kainate treatment had an opposite effect on levels and expression of EAAT2. Developmental studies indicated that the rapid regulation of transporter expression was not observed in rats younger than 21 days, an observation congruent 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 [3H]d-aspartate uptake. This study indicates that an early effect of kainate treatment consists of down-regulation of the neuronal transporter EAAT3 in restricted hippocampal regions, together with a modest increase in the expression of the glial transporter EAAT2. Differential regulation of neuronal and glial glutamate transporters may thus play a role in kainate-induced seizure, neurotoxicity and neuronal plasticity.
Neuroscience Program, Hedco Neuroscience Building, Room 309, University of Southern California, Los Angeles, CA 90089-2520, USA.
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Simantov
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Crispino
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Hoe
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Broutman
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Tocco
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Rothstein
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Baudry
D027322:Amino Acid Transport System X-AG; D000818:Animals; D001224:Aspartic Acid / Q000493:pharmacokinetics; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000503:physiopathology; D001923:Brain Chemistry / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D018690:Excitatory Amino Acid Agonists; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D050491:Glutamate Plasma Membrane Transport Proteins; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology; D007150:Immunohistochemistry; D007608:Kainic Acid; D008297:Male; D009457:Neuroglia / Q000737:chemistry / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D015345:Oligonucleotide Probes; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017981:Receptors, Neurotransmitter / Q000235:genetics* / Q000378:metabolism; D027981:Symporters; D014316:Tritium
D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D017981:Receptors, Neurotransmitter; C493398:Slc1a1 protein, rat; C493395:Slc1a2 protein, rat; D027981:Symporters; D014316:Tritium; D001224:Aspartic Acid; D007608:Kainic Acid