Cellular and Molecular Neurobiology

, Volume 14, Issue 5, pp 507–521

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

Authors

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

DOI: 10.1007/BF02088834

Cite this article as:
Chiasson, B.J., Armstrong, J.N., Hooper, M.L. et al. Cell Mol Neurobiol (1994) 14: 507. doi:10.1007/BF02088834

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-fosegr-1antisense oligodeoxynucleotides (ODNs)amygdala kindlingimmediate-early genesODN-induced toxicity
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Copyright information

© Plenum Publishing Corporation 1994