DIFFERENTIAL NPY MESSENGER-RNA EXPRESSION IN GRANULE CELLS AND INTERNEURONS OF THE RAT DENTATE GYRUS AFTER KAINIC ACID INJECTION

Using in situ hybridization histochemistry neuropeptide Y (NPY) mRNA e xpression was investigated after intraperitoneal injection of kainic a cid (KA) and after local application of KA or quinolinic acid into the dentate gyrus of the rat. Enhanced concentrations of NPY. mRNA were o bserved in interneurons of the hilus, including presumptive fusiform n eurons and pyramidal-shaped basket cells already 4 hours after initiat ion of limbic seizures by KA (10 mg/kg, i.p.). Increased NPY expressio n persisted in neurons resistant to seizure-induced cell death (6-48 h after i.p. KA). Exceptionally high hybridization signals were found i n interneurons of the hilus and the CA1 and CA3 sectors 8 months after KA-induced limbic seizures. In the granule cell layer only a transien t but pronounced increase in NPY mRNA was observed 12-24 h after injec tion. Only moderate changes were observed in this cell layer at later intervals. Anticonvulsant treatment with thiopental, after a brief per iod of generalized seizures, prevented the increase in NPY mRNA in gra nule cells but not in interneurons. No change in NPY message was found also in granule cells of rats which responded with mild ''wet dog sha ke'' behavior but not with motor seizures to KA injection.Local inject ions of low doses of KA (0.05-0.2 nmol) or quinolinic acid (65-100 nmo l) into the dentate gyrus of the hippocampus under deep thiopental ane sthesia, after 24 h, resulted in increased concentrations of NPY messa ge in interneurons of the ipsilateral, but not of the contralateral hi lus and not in granule cells. Higher doses of the excitatory amino aci d analogs caused partial neurodegeneration at the injection site, but enhanced NPY expression in interneurons of the contralateral dentate. Only the highest dose of quinolinic acid (100 nmol), resulting in gene ral neuronal cell loss at the injection area, induced enhanced NPY mRN A expression also in granule cells of the contralateral dentate gyrus. The experiments suggest different mechanisms for NPY mRNA expression in interneurons and in granule cells of the dentate gyrus. Whereas in the stratum granulosum NPY mRNA expression was only observed after gen eralized limbic seizures, in hilar interneurons it was augmented by on ly moderate neuronal stimulation or directly by KA. (c) 1994 Wiley-Lis s, Inc.