Changes in the Egr1 and Arc expression in brain structures of pentylenetetrazole-kindled rats

Epileptogenesis is regarded as a complicated and relatively poorly understood phenomenon. Some of immediate early genes (IEGs) as egr1 (zif268) or arc (arg3.1) are believed to play an important role in the process of epileptogenesis. However, how these genes are engaged in epilepsy is not fully elucidated.

In this study, we sought to explore how the spread of epileptiform activity (pentylenetetrazole (PTZ)-induced kindling) in the brain activates egr1, the early growth response gene, a member of the immediate early gene (IEG) family, and arc (activity-regulated cytoskeleton-associated protein) expression. We also wanted to map the specific brain regions that undergo kindling-related neuroplastic changes in rats.

When compared to animals that had been administered only a single PTZ injection (35 mg/kg), the animals at stage 5 of kindling had significantly higher Egr1 and Arc expression in the CA1 region of the hippocampus and the dentate gyrus. Increased expression of Egr1 was also observed in the CA3 region of the hippocampus, and Arc expression was also significantly higher in the entorhinal and the piriform cortices. The fastest and most potent increase in Egr1 expression during PTZ-induced kindling was found in the piriform and entorhinal cortices. The pattern of Arc expression was different than that of Egr1. The most prominent increase in Arc expression during kindling was present in the entorhinal cortex, the dentate gyrus, and the basolateral nucleus of the amygdala.

Our results demonstrate that the IEGs, egr1 and arc, may significantly contribute to synaptic reorganization induced by the kindling of seizures.