Cycloheximide inhibits kainic acid-induced GAP-43 mRNA in dentate granule cells in rats

WE have previously shown that kainic acid-induced seizures in adult rats caused an up-regulation of GAP-43 mRNA in the granule cells of the hippocampus, suggesting an involvement of this protein in the kainic acid-induced sprouting of messy fibres. To determine whether this effect was dependent on the synthesis of proteins activated under these experimental conditions we examined the effect of cycloheximide, a protein synthesis inhibitor, on kainic acid-induced GAP-43 mRNA. Cycloheximide, injected s.c. 2 h but not 8 h after kainic acid, markedly reduced the increased expression of GAP-43 mRNA in granule cells. These results suggest that a rapid mechanism involving new protein synthesis is activated by kainic acid to induce GAP-43 in the granule cells and possibly trigger the structural remodeling of messy fibres.