Kainic acid seizures cause enhanced expression of cholecystokinin-octapeptide in the cortex and hippocampus of the rat.
Immunocytochemistry and in situ hybridization techniques were used for investigating changes in cholecystokinin immunoreactivity and mRNA in the cerebral cortex and hippocampus after kainic acid-induced limbic seizures in the rat. Marked increases in cholecystokinin mRNA concentrations were observed in layers II/III and V/VI of the cerebral cortex, in CA1 pyramidal neurons of the hippocampus, and in presumptive basket cells of the dentate gyrus 1 and 2 days after the acute seizures. Whereas cholecystokinin mRNA contents returned to normal in the cerebral cortex and the CA1 sector at later intervals, high concentrations were observed in basket cells even 2 months after the initial seizures. Accordingly, cholecystokinin-like immunoreactivity was intensified in the cerebral cortex, CA1 sector and in presumed basket cells of the hippocampus 30 days after kainic acid. Besides its high content in basket cells, cholecystokinin-like immunoreactivity was primarily present in neuronal fibers or diffusely distributed in the respective brain area. In the hippocampus, strongly enhanced staining for cholecystokinin was also observed in the alveus, the stratum lacunosum moleculare, and in the inner molecular layer, suggesting increased concentrations of the peptide in afferent and efferent fibers of the hippocampus. The present experiments suggest a strong activation of cholecystokinin systems in the brain after kainic acid-induced limbic seizures in the rat. This is indicated by pronounced increases in cholecystokinin mRNA in the cortex and individual cell types of the hippocampus (basket cells, granule cells, and CA1 pyramidal neurons). The subsequent increases in cholecystokin immunoreactivity even surpass those in mRNA. The observed changes may be part of the self-defense mechanisms that protect the animals during subsequent epileptic episodes.
Gruber
B
B
Department of Pharmacology, University of Innsbruck, Austria.
Greber
S
S
Sperk
G
G
D000679:Amygdala / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010296:Parietal Lobe / Q000378:metabolism / Q000473:pathology; D011712:Pyramidal Tracts / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D012844:Sincalide / Q000032:analysis / Q000096:biosynthesis*
D012333:RNA, Messenger; D012844:Sincalide; D007608:Kainic Acid