Role of Glutamate and GABA Transporters in Development of Pentylenetetrazol-Kindling

Abstract

Kindling is a form of epileptogenesis that can be induced with pentylenetetrazol (PTZ). We undertook this study to evaluate the contribution of glutamate and GABA transporters to the process of PTZ kindling. Rats were injected i.p. three times per week with PTZ (40 mg/kg) until they were fully kindled. In rats who achieved full kindling, measurement of hippocampal glutamate and GABA transporters within 24 h by western blot showed that GLAST, GLT-1, and EAAC1 were elevated significantly. However, fully kindled rats at 30 days after their last seizure had no change in either glutamate or GABA transporters proteins. These sequential observations suggest that glutamate transporters may contribute to the occurrence of seizures, but were not associated with maintenance of epileptogenesis. During this experiment, we collected data from animals that had kindled easily and animals who were resistant to kindling. Easily-kindled rats reached full kindling with less than five injections of PTZ. Kindling resistant animals failed to achieve full kindling even after administration of 12 consecutive injections of PTZ. Levels of EAAC1 and GAT-1 in easily-kindled rats were decreased by 30% when compared to kindling resistant animals at 30 days after the last PTZ injection. Since decreased EAAC1 and GAT-1 would diminish GABA function, less quantity of these proteins would appear to be associated with the convulsive threshold at the beginning of kindling development. We wonder if glutamate and GABA transporters might be operant in a convulsion threshold set factor or as a pace factor for kindling.

Hippocampal GABA transporter distribution in patients with temporal lobe epilepsy and hippocampal sclerosis

“…Previous Western blot analyses of hippocampal tissue from various epilepsy models also demonstrated unchanged GAT-1 levels (Doi et al, 2005(Doi et al, , 2009Lee et al, 2006). As severe HS is characterized by an overall neuronal loss, a compensatory upregulation of GAT-1 in the remaining neurons may be expected.…”

Effect of GLT-1 modulator and P2X7 antagonists alone and in combination in the kindling model of epilepsy in rats

“…Microdialysate collected from hippocampus regions during seizures reveals an increase in the concentration of glutamate. Spillover of glutamate and accompanying neuronal excitation and impact of that amino acid on glutamate receptors, especially NMDA, are thought to be fundamental to the process of kindling [33]. Downregulation of GLT-1 transporters was also reported in PTZ-kindled animals, which decreases the glutamate uptake from the synaptic cleft [34].…”

Effects of Intravenous Human Umbilical Cord Blood Mesenchymal Stem Cell Therapy versus Gabapentin in Pentylenetetrazole-Induced Chronic Epilepsy in Rats

“…It is thought that the convulsant properties of PTZ are mainly due to an impairment of GABA-ergic neurotransmission [41]. Therefore, the possible role of GABA in the observed effects cannot be ignored.…”