Pentylenetetrazole-induced convulsions affect cellular and molecular parameters of the mechanism of action of triiodothyronine in adult rat brain

Abstract

The aim of the current study was to elucidate whether the response of the adult rat brain to thyroid hormones is affected by the intensity of neuronal activity. For this purpose, the kinetic characteristics of nuclear T 3 binding, the relative expression of thyroid hormone receptor (TR) isoforms and the synaptosomal content of thyroid hormones in adult rat brain were examined after administration of a single convulsion dose of pentylenetetrazole (PTZ). Experiments in adult Wistar rats revealed an increase (33%) of the density of specific T 3 nuclear receptors in cerebral hemispheres 4 h after PTZ-induced seizures while no changes were observed in the dissociation constant. The relative expression of the T 3-binding isoforms of TRs was not affected, while there was a gradual decrease of the relative expression of the TRα2 variant (non-T 3 binding isoform). The above changes were coupled with an increase of the synaptosomal T 3 levels during the epileptic seizures. Our study revealed inversely proportional changes between the nuclear T 3 binding sites and the TRα2 mRNA levels 4 h after PTZ-induced seizures, suggesting that the regulation of the expression of the non-T 3 binding variant of TRs determines the nuclear T 3 binding sites in adult rat brain, while the synaptosomal T 3 levels could play a novel functional role in the signaling from the synapse to the nucleus.