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 mossy 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 mossy fibres.
Bendotti
C
C
Laboratory of Neuropharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Pende
M
M
Guglielmetti
F
F
Samanin
R
R
D000818:Animals; D001345:Autoradiography; D003513:Cycloheximide / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism; D019922:GAP-43 Protein; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D003513:Cycloheximide; D007608:Kainic Acid