Alterations in glutamate transporter protein levels in kindling-induced epilepsy.
There is increasing evidence that levels of glutamate are elevated in certain brain regions immediately prior to and during induction and propagation of seizures. Modulation of high-affinity glutamate uptake is a potential mechanism responsible for the elevated levels observed with Seizures. To date, three distinct Na(+)-dependent glutamate transporters have been cloned from rat and rabbit: GLT-1, GLAST, and EAAC-1. We performed a series of experiments to determine whether levels of these transporters are altered in amygdala-kindled rats. Levels of GLT-1, GLAST, and EAAC-1 were examined in three brain regions (hippocampus, piriform cortex/amygdala, and limbic forebrain) by quantitative immunoblotting using subtype-specific antibodies. GLAST protein was down-regulated in the piriform cortex/amygdala region of kindled rats as early as 24 h after one stage 3 seizure and persisting through multiple stage 5 seizures. In contrast, kindling induced an increase in EAAC-1 levels in piriform cortex/amygdala and hippocampus once the animals had reached the stage 5 level. NO changes in GLT-1 were observed in any region examined. Changes in transporter levels could contribute to the changes in glutamate levels seen with kindling.
Miller
H P
HP
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, USA.
Levey
A I
AI
Rothstein
J D
JD
Tzingounis
A V
AV
Conn
P J
PJ
D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology; D002540:Cerebral Cortex / Q000737:chemistry / Q000503:physiopathology; D004827:Epilepsy / Q000209:etiology / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D006624:Hippocampus / Q000737:chemistry / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins