Developmental switch in phenotypic expression of preproenkephalin mRNA and 45Ca2+ accumulation following kainate-induced status epilepticus.
Kainic acid-induced status epilepticus results in delayed degeneration of CA3 hippocampal neurons in the mature but not immature rat hippocampus. In adult rats, the putative opioid precursor, preproenkephalin (PPE) mRNA increases in the dentate gyrus (DG), a region resistant to damage, following continuous limbic seizures. To explore why the immature brain is resistant to seizure-induced damage, the regional distribution of PPE mRNA expression and 45Ca2+ accumulation were compared in postnatal day 14 (P14) pup, and adult hippocampus at 5-6 h after kainate-induced status epilepticus. Inverted patterns of PPE expression and Ca2+ uptake were observed at the two ages. In P14 pups, PPE mRNA expression increased in DG and escalated in CA3, regions where 45Ca2+ accumulations were absent. In adult rats, PPE mRNA expression increased only in DG; 45Ca2+ labeling was predominant in CA3a,c and absent in DG. Pronounced increases in enkephalin neuropeptide synthesis in immature CA3 neurons may reduce glutamate release presynaptically and also prevent voltage-gated Ca2+ uptake into these neurons despite recurrent seizure activity. Opioid-mediated inhibition may provide an explanation for the resistance of the immature CA3 region to seizure-induced damage.
Friedman
L K
LK
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
D000818:Animals; D001345:Autoradiography; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D004745:Enkephalins / Q000096:biosynthesis*; D018690:Excitatory Amino Acid Agonists; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development; D017403:In Situ Hybridization; D007608:Kainic Acid; D010641:Phenotype; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*
D002132:Calcium Radioisotopes; D004745:Enkephalins; D018690:Excitatory Amino Acid Agonists; D011498:Protein Precursors; D012333:RNA, Messenger; C033660:preproenkephalin; D007608:Kainic Acid; D002118:Calcium