Cellular and Molecular Neurobiology

, Volume 14, Issue 5, pp 507–521

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
Article

Summary

1. Amphetamine-induced c-fos andegr-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.

Key words

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

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Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • B. J. Chiasson
    • 1
  • J. N. Armstrong
    • 1
    • 2
  • M. L. Hooper
    • 1
  • P. R. Murphy
    • 3
  • H. A. Robertson
    • 1
  1. 1.Laboratory of Molecular Neurobiology, Department of PharmacologyDalhousie UniversityHalifaxCanada
  2. 2.Department of Anatomy and NeurobiologyDalhousie UniversityHalifaxCanada
  3. 3.Department of Physiology and BiophysicsDalhousie UniversityHalifaxCanada

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