title: Decreased expression of glutamate transporters in genetic absence epilepsy rats before seizure occurrence.
abstract: In absence epilepsy, epileptogenic processes are suspected of involving an imbalance between GABAergic inhibition and glutamatergic excitation. Here, we describe alteration of the expression of glutamate transporters in rats with genetic absence (the Genetic Absence Epilepsy Rats from Strasbourg: GAERS). In these rats, epileptic discharges, recorded in the thalamo-cortical network, appear around 40 days after birth. In adult rats no alteration of the protein expression of the glutamate transporters was observed. In 30-day-old GAERS protein levels (quantified by western blot) were lower in the cortex by 21% and 35% for the glial transporters GLT1 and GLAST, respectively, and by 32% for the neuronal transporter EAAC1 in the thalamus compared to control rats. In addition, the expression and activity of GLAST were decreased by 50% in newborn GAERS cortical astrocytes grown in primary culture. The lack of modification of the protein levels of glutamatergic transporters in adult epileptic GAERS, in spite of mRNA variations (quantified by RT-PCR), suggests that they are not involved in the pathogeny of spike-and-wave discharges. In contrast, the alteration of glutamate transporter expression, observed before the establishment of epileptic discharges, could reflect an abnormal maturation of the glutamatergic neurone-glia circuitry.
authors.affiliation: INSERM U433, Faculté de Médecine Laënnec, Lyon, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Dutuit
authors.forename: Monique
authors.initials: M
authors.lastname: Touret
authors.forename: Raphaël
authors.initials: R
authors.lastname: Szymocha
authors.forename: Astrid
authors.initials: A
authors.lastname: Nehlig
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Belin
authors.forename: Marianne
authors.initials: M
authors.lastname: Didier-Bazès
mesh_terms: D000375:Aging / Q000378:metabolism; D027322:Amino Acid Transport System X-AG / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D000918:Antibody Specificity; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000235:genetics / Q000378:metabolism*; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D006624:Hippocampus / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000209:etiology / Q000378:metabolism*; D027981:Symporters; D013788:Thalamus / Q000378:metabolism
chemical_list: D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D012333:RNA, Messenger; C493398:Slc1a1 protein, rat; C493392:Slc1a3 protein, rat; D027981:Symporters