INCREASED EXPRESSION OF GAP-43, SOMATOSTATIN AND NEUROPEPTIDE-Y MESSENGER-RNA IN THE HIPPOCAMPUS DURING DEVELOPMENT OF HIPPOCAMPAL KINDLINGIN RATS

The expression and distribution of the mRNA coding for the growth-asso ciated protein-43 (GAP-43), a putative marker for neuritic growth, for preprosomatostatin and the preproneuropeptide Y (ppNPY) were analysed in the rat hippocampus during the development of hippocampal kindling by an in situ hybridization technique and computer-assisted grain cou nting in the cell. The levels of GAP-43 mRNA increased significantly i n the CA3 pyramidal neurons and hilar polymorphic neurons of the denta te gyrus 2 days after stage 2 of kindling (preconvulsive stage) but no t stage 5 (full seizure expression) in the stimulated hippocampus. The distribution of GAP-43 mRNA was the same in the hippocampus of kindle d rats as in sham-stimulated animals. Preprosomatostatin mRNA and ppNP Y mRNA contents rose significantly in the hilar polymorphic neurons of the dentate gyrus of the stimulated and contralateral hippocampus at both stages of kindling, with the greatest effect at stage 5. In addit ion, the number of ppNPY mRNA neurons in the fascia dentata was signif icantly higher in kindled rats than in controls, but there were no dif ferences in the number of preprosomatostatin mRNA-positive cells. Prep rosomatostatin and ppNPY mRNAs were also increased in the neurons of t he stratum oriens of the CA1 - CA3 subfield of fully kindled animals, whereas at stage 2 only neurons of the CA1 stratum oriens showed a sig nificant increase of preprosomatostatin mRNA. No changes in preprosoma tostatin and ppNPY mRNA expression were observed in the various region s of the hippocampus after a single afterdischarge or 1 month after st age 5. These data show that synthesis of somatostatin and neuropeptide Y increases in certain neurons of the hippocampus during the developm ent of hippocampal kindling, and support the suggestion that these pep tides are involved in epileptogenesis. Moreover, the increased synthes is of GAP-43 may contribute to the synaptic remodelling of certain hip pocampal neurons during kindling.