Sequential changes in glutamate transporter mRNA levels during Fe(3+)-induced epileptogenesis.
Severe head injury in humans can cause recurrent seizures; this form of epilepsy appears to correlate with the occurrence of parenchymal hemorrhage. The injection of ferric cations, one component of hemoglobin, into rat amygdala, causes lipid peroxidation, and recurrent spontaneous seizures. We wondered whether the regulation of glutamate might be perturbed as a result of severe head injury, which might then act as a mechanism of chronic epileptogenesis. Levels of glutamate transporter glutamate-aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), and excitatory amino-acid carrier (EAAC-1) mRNA were measured in ipsilateral and contralateral hippocampi and cerebral cortex removed from rats at 60 min, 24 h, and 5, 15 and 30 days after FeCl(3) injection into the amygdaloid body. While the neuronal transporter EAAC-1 mRNA was elevated bilaterally for up to 30 days following the microinjection that initiated seizures, GLT-1 mRNA, derived from glial cells, returned to basal levels. At 15 and 30 days after injection, however, when the experimental animals were experiencing spontaneous limbic behavioral seizures, GLAST mRNA was down-regulated. Epileptogenesis may correlate with the impairment of glial glutamate transport, leading to an excitation and imbalance of transmitter influences within the hippocampi and cerebral cortex.
Doi
T
T
Department of Psychiatry, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki, Japan.
Ueda
Y
Y
Tokumaru
J
J
Mitsuyama
Y
Y
Willmore
L J
LJ
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002540:Cerebral Cortex / Q000378:metabolism; D002712:Chlorides; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D027341:Excitatory Amino Acid Transporter 1; D005290:Ferric Compounds / Q000494:pharmacology*; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects*; D050491:Glutamate Plasma Membrane Transport Proteins; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters; D013997:Time Factors; D014158:Transcription, Genetic
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D002712:Chlorides; D027341:Excitatory Amino Acid Transporter 1; D005290:Ferric Compounds; D050491:Glutamate Plasma Membrane Transport Proteins; D012333:RNA, Messenger; C493392:Slc1a3 protein, rat; D027981:Symporters; C024555:ferric chloride