Functional role for redox in the epileptogenesis: molecular regulation of glutamate in the hippocampus of FeCl3-induced limbic epilepsy model.
We used western blotting to measure the quantity of glutamate and gamma-aminobutyric acid (GABA) transporters proteins within hippocampal tissue obtained from rats who had undergone epileptogenesis. Chronic seizures were induced by amygdalar injection of FeCl(3). We found that the glial glutamate transporters GLAST and GLT-1 were down-regulated at 60 days after initiation of chronic and recurrent seizures. However, the neuronal glutamate transporter EAAC-1 and the GABA transporter GAT-3 were increased. We performed in vivo microdialysis in freely moving animals to estimate in vivo redox state. We found that the hippocampal tissues were oxidized, resulting in even further impairment of glutamate transport. Our data show that epileptogenesis in rats resulting in chronic and recurrent seizures is associated with collapse of glutamate regulation caused by both the molecular down-regulation of glial glutamate transporters combined with the functional failure due to oxidation.
Ueda
Yuto
Y
Section of Psychiatry, Department of Clinical Neuroscience, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. usan@med.miyazaki-u.ac.jp
Doi
Taku
T
Nagatomo
Keiko
K
Willmore
L James
LJ
Nakajima
Akira
A
D000818:Animals; D001522:Behavior, Animal; D002712:Chlorides; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005290:Ferric Compounds; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
D002712:Chlorides; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D005290:Ferric Compounds; D018698:Glutamic Acid; C024555:ferric chloride