Evidence for Fos involvement in the regulation of proenkephalin and prodynorphin gene expression in the rat hippocampus.

For a long time Fos has been proposed to play some role in regulation of the proenkephalin (PENK) and prodynorphin (PDYN) gene expression. In recent years, however, evidence has accumulated that the transcription of both genes in several brain regions in vivo is transactivated by the transcription factor CREB rather than by Fos. In the present study, involvement of Fos in the mechanism of the PENK and PDYN gene induction in the hippocampal dentate gyrus during seizures elicited by kainic acid was studied using a knock-down technique. Pretreatment with an antisense oligonucleotide complementary to c-fos mRNA did not influence the kainic acid-elicited convulsions. It inhibited, by about 50%, the induction of Fos protein in the dentate gyrus during seizures. The subsequent induction of PENK and PDYN mRNAs was reduced by more than 60% by the c-fos antisense oligonucleotide, while constitutive expression of three other genes (alpha-tubulin, NMDA receptor-1, and GS protein alpha-subunit) was not affected. The obtained results support the view that Fos may be involved in regulation of the PENK and PDYN gene expression in the dentate gyrus during seizures, which further suggests that the mechanisms triggering the up-regulation of both these genes in the dentate gyrus may differ from these working in other brain regions, such as the striatum and hypothalamus.