Increased expression of the neuronal glutamate transporter (EAAT3/EAAC1) in hippocampal and neocortical epilepsy.
OBJECTIVE
To define the changes in gene and protein expression of the neuronal glutamate transporter (EAAT3/EAAC1) in a rat model of temporal lobe epilepsy as well as in human hippocampal and neocortical epilepsy.


METHODS
The expression of EAAT3/EAAC1 mRNA was measured by reverse Northern blotting in single dissociated hippocampal dentate granule cells from rats with pilocarpine-induced temporal lobe epilepsy (TLE) and age-matched controls, in dentate granule cells from hippocampal surgical specimens from patients with TLE, and in dysplastic neurons microdissected from human focal cortical dysplasia specimens. Immunolabeling of rat and human hippocampi and cortical dysplasia tissue with EAAT3/EAAC1 antibodies served to corroborate the mRNA expression analysis.


RESULTS
The expression of EAAT3/EAAC1 mRNA was increased by nearly threefold in dentate granule cells from rats with spontaneous seizures compared with dentate granule cells from control rats. EAAT3/EAAC1 mRNA levels also were high in human dentate granule cells from patients with TLE and were significantly elevated in dysplastic neurons in cortical dysplasia compared with non-dysplastic neurons from postmortem control tissue. No difference in expression of another glutamate transporter, EAAT2/GLT-1, was observed. Immunolabeling demonstrated that EAAT3/EAAC1 protein expression was enhanced in dentate granule cells from both rats and humans with TLE as well as in dysplastic neurons from human cortical dysplasia tissue.


CONCLUSIONS
Elevations of EAAT3/EAAC1 mRNA and protein levels are present in neurons from hippocampus and neocortex in both rats and humans with epilepsy. Upregulation of EAAT3/EAAC1 in hippocampal and neocortical epilepsy may be an important modulator of extracellular glutamate concentrations and may occur as a response to recurrent seizures in these cell types.
Crino
Peter B
PB
PENN Epilepsy Center, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jin
Hong
H
Shumate
Melissa D
MD
Robinson
Michael B
MB
Coulter
Douglas A
DA
Brooks-Kayal
Amy R
AR
D000293:Adolescent; D000328:Adult; D027322:Amino Acid Transport System X-AG; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000002:abnormalities / Q000378:metabolism; D002648:Child; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism*; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D005260:Female; D050491:Glutamate Plasma Membrane Transport Proteins; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D019579:Neocortex / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D027981:Symporters; D014018:Tissue Distribution
D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D012333:RNA, Messenger; C493400:SLC1A1 protein, human; C493397:SLC1A2 protein, human; C493398:Slc1a1 protein, rat; C493395:Slc1a2 protein, rat; D027981:Symporters