The application of antisense oligonucleotide technology to the brain: Some pitfalls

B. J. Chiasson, J. N. Armstrong, M. L. Hooper, P. R. Murphy, H. A. Robertson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

1. Amphetamine-induced c-fos and egr-1 expression in the striatum was used as a model in which to study the effects of antisense oligodeoxynucleotides (ODNs) directed at c-fos. Using direct infusions of ODNs into the striata of animals we have demonstrated that c-fos antisense ODNs retain most of their biological activity with 2- or 3-base substitutions. The c-fos antisense and mismatch ODNs attenuated Fos immunoreactivity but had little effect on Egr-1 immunoreactivity. 2. In another group of studies examining the role of c-fos in amygdala kindling, we have demonstrated that ODNs cause neurotoxic damage following repeated daily infusions into the amygdala. The damage observed was greatly diminished when the time interval between infusions was extended.

Original languageEnglish (US)
Pages (from-to)507-521
Number of pages15
JournalCellular and molecular neurobiology
Volume14
Issue number5
DOIs
StatePublished - Oct 1994
Externally publishedYes

Keywords

  • ODN-induced toxicity
  • amygdala kindling
  • antisense oligodeoxynucleotides (ODNs)
  • c-fos
  • egr-1
  • immediate-early genes

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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