Thyrotropin-releasing hormone gene expression and receptors are differentially modified in limbic foci by seizures.
Previous studies using two seizure paradigms, electroconvulsive 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 occurred 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 epilepsy by modulating excitatory processes.
Department of Anatomy, Indiana University School of Medicine, Indianapolis 46202-5120.
M J
MJ
Kubek
S M
SM
Knoblach
N A
NA
Sharif
D R
DR
Burt
G G
GG
Buterbaugh
K S
KS
Fuson
D000818:Animals; D001345:Autoradiography; D015536:Down-Regulation; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008032:Limbic System / Q000378:metabolism / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D018025:Receptors, Thyrotropin-Releasing Hormone; D012640:Seizures / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics*
D012333:RNA, Messenger; D017981:Receptors, Neurotransmitter; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone