Sequential changes in glutamate transporter protein levels during Fe(3+)-induced epileptogenesis.
Severe head injury in humans causes recurrent seizures; this form of epilepsy appears to correlate with occurrence of parenchymal hemorrhage. Injection of ferric cations, one component of hemoglobin, into rat amygdala, causes lipid peroxidation, and recurrent spontaneous seizures. We wondered whether regulation of extracellular glutamate might be perturbed as a mechanism of chronic epileptogenesis, therefore levels of glutamate transporter proteins GLT-1, GLAST and EAAC-1 were measured in ipsilateral and contralateral hippocampi removed from rats having spontaneous iron-induced limbic seizures. The neuronal transporter EAAC-1 was elevated bilaterally up to 30 days following the microinjection that initiated seizures. The neuronal transporter EAAC-1 was elevated bilaterally up to 30 days following the microinjection that initiated seizures. The glial transporter GLT-1 increased 5 and 15 days after iron injection on the side contralateral to the injection then returned to basal levels 30 days after the lesion. GLAST also showed an initial increase but at 15 and 30 days after injection, when experimental animals were experiencing spontaneous limbic behavioral seizures, this protein was down-regulated. The results suggest that iron-induced epileptogenesis involves alteration in glial glutamate transport that may lead to enhanced excitation within the hippocampus.
Ueda
Y
Y
Department of Psychiatry, Miyazaki Medical College, Miyazaki-Gun, Kihara 5200, Kiyotake-cho, Miyazaki, Japan. usan@post1.miyazaki-med.ac.jp
Willmore
L J
LJ
D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects*; D002352:Carrier Proteins / Q000032:analysis; D002712:Chlorides; D003292:Convulsants; D003720:Densitometry; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism*; D027341:Excitatory Amino Acid Transporter 1; D005290:Ferric Compounds; D050491:Glutamate Plasma Membrane Transport Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters; D009435:Synaptic Transmission / Q000187:drug effects
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D002712:Chlorides; D003292:Convulsants; D027341:Excitatory Amino Acid Transporter 1; D005290:Ferric Compounds; D050491:Glutamate Plasma Membrane Transport Proteins; C493392:Slc1a3 protein, rat; D027981:Symporters; C024555:ferric chloride