Pentylenetetrazole-induced convulsions affect cellular and molecular parameters of the mechanism of action of triiodothyronine in adult rat brain.
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 T3 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 T3 nuclear receptors in cerebral hemispheres 4h after PTZ-induced seizures while no changes were observed in the dissociation constant. The relative expression of the T3-binding isoforms of TRs was not affected, while there was a gradual decrease of the relative expression of the TR alpha2 variant (non-T3 binding isoform). The above changes were coupled with an increase of the synaptosomal T3 levels during the epileptic seizures. Our study revealed inversely proportional changes between the nuclear T3 binding sites and the TR alpha2 mRNA levels 4 h after PTZ-induced seizures, suggesting that the regulation of the expression of the non-T3 binding variant of TRs determines the nuclear T3 binding sites in adult rat brain, while the synaptosomal T3 levels could play a novel functional role in the signaling from the synapse to the nucleus.
Bolaris
Stamatis
S
Department of Human Reproduction, Helena Venizelou Hospital, 2 Venizelou Sqr., 11521 Athens, Greece.
Constantinou
Caterina
C
Valcana
Theony
T
Margarity
Marigoula
M
D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007456:Iodine Isotopes / Q000494:pharmacology; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology*
D007456:Iodine Isotopes; D012333:RNA, Messenger; D014284:Triiodothyronine; D010433:Pentylenetetrazole