Response of Voltage-Gated Sodium and Calcium Channels Subtypes on Dehydroepiandrosterone Treatment in Iron-Induced Epilepsy.

Abstract

Epilepsy is a neurological disorder characterized by the occurrence of spontaneous and recurrent seizures. In post-traumatic epilepsy (PTE), the mechanism of epileptogenesis is very complex and seems to be linked with voltage-gated ion channels. Dehydroepiandrosterone (DHEA), a neurosteroid have shown beneficial effect against various neurological disorders. We investigated antiepileptic effect of DHEA with respect to expression of voltage-gated ion channels subtypes in iron-induced epilepsy. Iron (FeCl3) solution was intracartically injected to induce epilepsy in rats and DHEA was intraperitoneally administered for 21days. Results showed markedly increased epileptiform seizures activity along with up-regulation of Nav1.1 and Nav1.6, and down-regulation of Cav2.1α at the mRNA and protein level in the cortex and hippocampus of epileptic rats. Moreover, the study demonstrated that these channels subtypes were predominantly expressed in the neurons. DHEA treatment has countered the epileptic seizures, down-regulated Nav1.1 and Nav1.6, and up-regulated Cav2.1α without affecting their cellular localization. In conclusion, the present study demonstrates antiepileptic potential of DHEA, escorted by regulationof Nav1.1, Nav1.6, and Cav2.1α subtypes in the neurons of iron-induced epileptic rats.