Differential regulation of mRNAs for neuropeptide Y and its receptor subtypes in widespread areas of the rat limbic system during kindling epileptogenesis

Expression of mRNAs for neuropeptide Y (NPY) and its receptor subtypes Y1 ( Y1-R), Y2 (Y2-R) and Y5 (Y5-R) was studied in adult rat brain using in situ hybridization after 40 rapidly recurring seizures induced with 5-min inter val by hippocampal kindling stimulations. At 2-4 h post-seizure, NPY mRNA l evels were markedly elevated in dentate granule cells, CAI and CA3 pyramida l layers, amygdala and piriform and entorhinal cortices. Gene expression ha d returned to control level in the dentate granule cell layer at 48 h but r emained high in the other areas, reaching baseline at 1 week. Transient dec reases of Y1-R mRNA levels were detected at 2-4 h in hippocampal subregions , amygdala, piriform, entorhinal and somatosensory cortices. The Y2-R mRNA levels were reduced at 2-4 h in the CA3 region and piriform cortex, but exh ibited marked increases at 48 h and 1 week post-seizure in the dentate gyru s, amygdala and piriform and entorhinal cortices. At 3 weeks, Y2-R mRNA exp ression had virtually returned to baseline. Elevated Y5-R mRNA levels were only detected at 2-4 h and confined to dentate granule cell layer and pirif orm and entorhinal cortices. These results demonstrate a cell- and region-s pecific, differential regulation of mRNA expression for NPY and Y1-R, Y2-R, and Y5-R in the limbic system following recurring seizures. Because the ge ne changes were transient, it seems unlikely that the presumed alterations of the corresponding proteins are involved in the maintenance of the epilep tic syndrome, which develops up to 4 weeks post-seizure in the present mode l and is stable thereafter. Our data provide further support for the hypoth esis that the changes of NPY and its receptors act to dampen seizure suscep tibility, and suggest that the cascade of gene changes is orchestrated to o ptimize this anticonvulsant effect. (C) 1999 Elsevier Science B.V. All righ ts reserved.