Expression of c-fos mRNA in the Hippocampus of Pentylenetetrazol Kindling Rat

ABSTRACT

Kindling, induced by repeated subconvulsive electrical or chemical stimulations, leads to progressive and permanent amplification of seizure activity, resulting in permanent brain changes. It is a good animal model of epilepsy and neural plasticity. C-fos has been proposed as the gene responsible for turning on molecular events for these permanent brain changes underlying epilepsy and neural plasticity. But the role of c-fos in the development of kindling is controversial. This study was undertaken to investigate the role of c-fos mRNA in the plastic changes underlying kindling. Among 66 adult male Sprague-Dawley rats, 29 rats were kindled by repeated administrations of subconvulsive doses (IS-25 mg/kg) of pentylenetetrazol (PTZ), 25 rats experienced convulsions induced by a single injection of convulsive dose(30-60 mg/kg) of PTZ, and 12 rats experienced convulsions by a single electroconvulsive shock (ECS), Twelve control rats received normal saline only. Animals were sacrificed at various seizure stages. C-fos mRNA levels in the hippocampus were quantified using slot-blot hybridization analysis. In the experiment of PTZ kindling, c-fos mRNA expression 30 min after convulsion was elevated about 2-4 times at stage 1, 2 and 5, but wasn't increased at stage 3 and 4, compared with controls. C-fos mRNA expression 60 min after convulsion was elevated about 2 times at stage 1 and 5, but wasn't increased at stage 2, 3 and 4. In the experiment of PTZ-induced seizures, c-fos mRNA expression 30 min after convulsion was elevated 2.5, 2.2 and 6 times stage 1-2, 3-4, and 5, respectively. C-fos mRNA expression 60 min after convulsion was elevated 3.6 times at stage 3-4, but wasn't increased at stage 2 and 5. In the experiment of ECB-induced seizures, c-fos mRNA expression 1 min after mild convulsion was elevated 3,3 times, but wasn't increased generalized tonic-clonic seizure. C-fos mRNA expression 60 min after convulsion wasn't increased at any stage of convulsion. These results show that c-fos mRNA levels have no meaningful relationship with the stages of PTZ kindling, and PTZ or ECS-induced seizures, and that c-fos mRNA does not seem to play the crucial role in turning on a molecular program underlying kindling.