NEUROPEPTIDES-IMMUNOREACTIVITY AND THEIR MESSENGER-RNA EXPRESSION IN KINDLING - FUNCTIONAL IMPLICATIONS FOR LIMBIC EPILEPTOGENESIS

Recent studies have demonstrated that neuropeptide expression in foreb rain neurons is responsive to changes in physiological activity. This is particularly true in the hippocampus where the expression of variou s neuropeptides has been reported to change in distinct neuronal popul ations in response to seizure activity. The aim of this work is to rev iew and integrate the information on the pathological changes and func tional modifications in neuropeptide systems of the hippocampal format ion in kindling and other models of limbic epilepsy. This will be done by presenting a study in which we investigated the changes in the exp ression of somatostatin, neuropeptide Y (NPY), neurokinin B (NKB) and cholecystokinin-octapeptide (CCK) in the rat hippocampal principal neu rons during and after kindling of the hippocampus using immunocytochem istry and in situ hybridization analysis of mRNA. NPY-IR was transient ly expressed in the granule cells/mossy fibres after the preconvulsive stage 2 and 2 days but not 1 week after three consecutive tonic-cloni c seizures (stage 5). A more pronounced increase was observed in NKB-I R lasting for 1 week after kindling acquisition. Only the NKB mRNA exp ression was enhanced in granule cells at these intervals. At stages 2 and 5, somatostatin- and NPY-IR and their mRNA levels were markedly in creased in interneurons in the deep hilus and in the polymorphic cell layer and their presumed projections to the outer molecular layer of t he dentate gyrus. NKB- and CCK-IR and their mRNAs were highly expresse d in basket cells at both stages of kindling. Their IR was increased i n the inner molecular layer of the dentate gyrus in the ventral hippoc ampus. peptide-containing neurons in the hilus appeared well preserved in spite of a reduction of Nissl stained cells by 24% in the stimulat ed and contralateral hippocampus at stage 5. In the hippocampus proper , somatostatin and NPY-IR were enhanced in the stratum lacunosum molec ulare while CCK-IR Fibres and its mRNA were particularly expressed in the pyramidal cell layer. The number of somatostatin-, NKB- and CCK-IR cells was increased in the subiculum. The intensity of these changes was similar 2 days after stages 2 or 5 of kindling. Less pronounced ef fects were observed 1 week after kindling completion. These results, i n the frame of the literature data, suggest that lasting functional ch anges occur in distinct neuropeptide-containing neurons during limbic epileptogenesis. This may have profound effects on synaptic transmissi on and contribute to modulate hippocampal excitability.