Thyroid hormones: Possible roles in epilepsy pathology
The expression of mRNA coding for prepro-thyrotropin releasing hormone (preproTRH) was estimated in the rat brain in two animal models of limbic seizures, evoked by systemic administration of pilocarpine (400 mg/kg ip) or kainate (12 mg/kg ip). As shown by an in situ hybridization study, after 24 h both pilocarpine- and kainate-induced seizures profoundly increased the preproTRH mRNA level in the dentate gyrus. After 72 h, the preproTRH mRNA level was back to control values. Kainate-treated rats showed an elevated level of TRH in the hippocampus, septum, frontal and occipital cortex after 24 and 72 h, whereas in the striatum and amygdala the TRH level was raised after 72 h only. In the hypothalamus, TRH levels was lowered after 3 and 24 h, and returned to the control after 72 h. Pilocarpine-induced seizures also elevated the TRH level after 72 h in the majority of the above structures, except for the hypothalamus and amygdala where no changes were found at any time point. A radioreceptor assay showed that kainate decreased the Bmax value of TRH receptors in the striatum and hippocampus after 3 and 24 h, respectively, and had no effect on the Kd values. In contrast, pilocarpine-induced seizures lowered the Bmax of TRH receptors in the striatum, hippocampus and piriform cortex after 72 h only, and decreased Kd values in the striatum, amygdala and frontal cortex. These data showed that pilocarpine- and kainate-induced seizures enhanced likewise preproTRH mRNA in the dentate gyrus; on the other hand, they differed with respect to time- and structure-related changes in TRH tissue levels and TRH receptors. These differences may have functional significance in TRH-dependent control mechanism of the seizure activity in these two models of limbic epilepsy.