Differential regulation of neuropeptide and proto-oncogene mRNA content in the hippocampus following recurrent seizures.
The amounts of the mRNAs for the neuropeptide precursor proteins preproenkephalin, preprocholecystokinin and preproneuropeptide Y were measured in the entorhinal cortex of normal rats and rats that had experienced recurrent limbic seizures induced by a small contralateral lesion of the dentate gyrus hilus. Additionally, the amount of mRNAs for preproenkephalin as well as for the cellular proto-oncogenes c-myc, c-fos and c-H-ras, which are thought to be mediators of intracellular signal transduction, was determined in hippocampus in these same animals. It was determined that the hilus lesion led to a dramatic (18-fold) increase in the content of preproenkephalin mRNA in the entorhinal cortex whereas only a modest increase in preproneuropeptide Y mRNA content and no change in preprocholecystokinin mRNA was detected in this same brain region. In hippocampus a large and very rapid increase in c-fos mRNA was observed to precede the previously reported increase in preproenkephalin mRNA following hilus lesion-induced seizures. Like the increase in opioid peptide mRNA, the increase in c-fos mRNA began early in the period of seizure activity and could be blunted by maintaining the animals under anesthesia with the anticonvulsant sodium pentobarbital. Messenger RNA for c-H-ras was not altered at any time following the lesion and c-myc mRNA was not reliably detected in either control or hilus lesioned rats. These data demonstrate that neuropeptide genes within the entorhinal cortex and proto-oncogenes within the hippocampus are differentially regulated by seizure activity and suggest that the c-fos proto-oncogene may be involved in events which mediate the physiological regulation of enkephalin gene expression.
Division of Endocrinology, SUNY Stony Brook 11794.
J D
JD
White
C M
CM
Gall
D000758:Anesthesia; D000818:Animals; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008032:Limbic System / Q000378:metabolism; D008297:Male; D009479:Neuropeptides / Q000235:genetics*; D009857:Oncogenes; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012008:Recurrence; D012640:Seizures / Q000378:metabolism*
D009479:Neuropeptides; D011498:Protein Precursors; D012333:RNA, Messenger