Involvement of a c-fos-dependent mechanism in caffeine-induced expression of the preprotachykinin A and neurotensin/neuromedin N genes in rat striatum

The European Journal of Neuroscience
P SvenningssonBertil B Fredholm

Abstract

Striatal c-fos induction was blocked by local administration of phosphorothioated c-fos antisense oligonucleotides (AS-ODN) to examine the possible role of caffeine-induced c-fos expression in transcriptional regulation of striatal preproenkephalin, prodynorphin, preprotachykinin A and neurotensin/neuromedin N. Caffeine (100 mg/kg i.p.) induced both c-fos mRNA and Fos-protein, and this induction was significantly attenuated by intrastriatal injection of 4 (but not 1) nmol c-fos AS-ODN. This suggests that, in addition to translational arrest, other mechanisms may be involved in the mediation of antisense action. The action of the AS-ODN was sequence specific. The antisense blockade of c-fos reduced the effect of caffeine on the expression of mRNAs for preprotachykinin A and neurotensin/neuromedin N in the ventrolateral caudate-putamen. Levels of preproenkephalin and prodynorphin transcripts were unaffected. Thus caffeine induction of striatal preprotachykinin A mRNA and neurotensin/neuromedin N mRNA, but not of preproenkephalin mRNA or prodynorphin mRNA, may at least in part be mediated by a pathway involving Fos protein. The findings illustrate the utility of blockade of gene expression with antisense oligonucleotides for in vi...Continue Reading

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Citations

Sep 29, 1999·Progress in Neurobiology·P SvenningssonB B Fredholm
Apr 7, 1999·Antisense & Nucleic Acid Drug Development·A W Szklarczyk, L Kaczmarek
Jan 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Douglas S Kim, Richard D Palmiter
Nov 15, 2017·Neurotoxicity Research·Anna Maria GórskaKrystyna Gołembiowska

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