Increases in thyrotropin-releasing hormone messenger RNA expression induced by a model of human temporal lobe epilepsy: effect of partial and complete kindling

Abstract

Thyrotropin-releasing hormone and its receptor are differentially distributed throughout the limbic forebrain. In addition to its neuroendocrine function, several non-endocrine central nervous system effects of thyrotropin-releasing hormone and its analogs have been reported, including anticonvulsant effects in animals and humans. Kindling, as a model of temporal lobe epilepsy, produces elevations of endogenous thyrotropin-releasing hormone specifically in seizure-prone limbic regions. The present study used semi-quantitative in situ hybridization to characterize changes in thyrotropin-releasing hormone messenger RNA that occurred during the kindling process (partial kindling), as well as after fully kindled seizures. No significant change in thyrotropin-releasing hormone messenger RNA was detected 1 h postictally, whereas significant elevations were detected in the granule cell layer of the hippocampal dentate gyrus, diffuse nuclei of the amygdala and in layers II and III of piriform and entorhinal cortices from 3 to 48 h after a single generalized seizure in fully kindled rats. Peak messenger RNA expression occurred from 6 to 12 h postictally, with a decline at 24 h, followed by a precipitous return to undetectable levels by 48 h, except in the dentate gyrus. In marked contrast, partial kindling produced no detectable change in thyrotropin-releasing hormone messenger RNA by 6 h after the first occurrence of stage 1–5 seizures. Electrode placement, a single afterdischarge, or a 20-μA stimulation of the amygdala was not associated with accumulation of thyrotropin-releasing hormone messenger RNA. Thus, only fully kindled generalized seizures increased thyrotropin-releasing hormone messenger RNA expression in identical limbic regions which also showed postictal elevations in thyrotropin-releasing hormone. However, this enhancement followed a more immediate and shorter lasting time-course than previously demonstrated increases in the tripeptide. These results support the hypothesis that thyrotropin-releasing hormone is an important neuromodulator in epileptic foci.