Thyrotropin‐Releasing hormone gene expression and receptors are differentially modified in limbic foci by seizures

Abstract

Previous studies using two seizure paradigms, electronconvulsive shock and kindling, suggested potential sites of endogenous thyrotropin-releasing hormone (TRH) action in specific epileptogenic areas. We studied TRH gene expression and TRH receptors in rat limbic areas using the kindling model of epilepsy. Immunoassayable TRH increased 4- to 20-fold over control levels in specific subregions of the hippocampus 24 hours after a single stage 5 seizure. Concurrently, TRH receptor binding was significantly reduced in hippocampal (23–39%) and amygdaloid (21–22%) membranes. Dramatic temporal and spatial changes in prepro-TRH messenger RNA were visualized by in situ hybridization histochemistry in the hippocampal dentate gyrus, the piriform cortex, and the amygdala. Peak hybridization occured 6 and 12 hours postictally in these loci and returned toward basal levels by 24 hours. These results are consistent with the hypothesis that TRH may have an important role in the pathophysiology of epilepsy by modulating excitatory processes.