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Antisense Therapeutics in the Central Nervous System

The Induction of c-fos
  • Bernard J. Chiasson
  • Murray Hong
  • Michele L. Hooper
  • John N. Armstrong
  • Paul R. Murphy
  • Harold A. Robertson
Part of the Methods in Molecular Medicine book series (MIMM, volume 1)

Abstract

Immediate-early genes (IEGs) are members of a class of genes that respond, in many cell types, to a variety of stimuli by rapid, but transient expression (1). Several of these IEGs code for transcription factors and include the widely studied activator protein-1 (AP-1) transcription factor complex believed to be homo- and heterodimeric assemblies of the Fos and Jun families (1–3). IEGs are induced in the central nervous system (CNS) by diverse physiological and pharmacological stimuli, many of which, when presented once or on multiple occasions, can alter the “normal” functioning of the brain in a permanent or semipermanent fashion. Examples of pharmacological stimuli that lead to long-term changes are the highly addictive psychostimulant drugs, amphetamine and cocaine These drugs produce a robust activation of IEGs (e.g., c-fos, jun-B, egr-1) in areas of the brain that are believed to be part of the neural substrates of addiction (4–8) In animal models of epileptogenesis or memory, such as kindling and long-term potentiation (LTP), respectively, electrical stimuli produce activation of IEGs within the brain structures thought to underlie the long-lasting changes associated with these experimental procedures (9–16). IEGs can also be induced by noninvasive stimuli, such as a simple light pulse given to animals in a dark room. The circadian rhythms of animals that are housed in darkened conditions can be shifted by exposing them to a light during then subjective night. Activation of IEGs in such experiments are restricted to the suprachiasmatic nucleus (SCN), which is believed to be the seat of the biological clock (17).

Keywords

Rotational Behavior Antisense ODNs Antisense Technology Pharmacological Stimulus Amygdala Kindling 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Curran, T. and Morgan, J I (1995) Fos’ an immediate-early transcription factor in neurons. J Neurobiol 26, 403–412PubMedCrossRefGoogle Scholar
  2. 2.
    Curran, T and Franza, B. R., Jr (1988) Fos and Jun’ the AP-1 connection Cell 55, 395–397PubMedCrossRefGoogle Scholar
  3. 3.
    Morgan, J. I. and Curran, T (1991) Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jan Annu Rev Neurosci 14, 42l–451.CrossRefGoogle Scholar
  4. 4.
    Graybiel, A M., Moratalla, R., and Robertson, H A. (1990) Amphetamine and cocaine induce drug-specific activation of the c-fos gene in striosome-matrix compartments and limbic subdtvisions of the striatum Proc. Natl Acad Sci USA 87, 6912–6916PubMedCrossRefGoogle Scholar
  5. 5.
    Moratalla, R., Robertson, H A., and Graybiel, A M. (1992) Dynamic regulation of NGFZ-A (zif268, egr 1) gene expression in the striatum. J Neurosci. 12, 2609–2622PubMedGoogle Scholar
  6. 6.
    Moratalla, R., Vickers, E A., Robertson, H A., Cochran, B H., and Graybiel, A M. (1993) Coordinate expression of c-fos and junB is induced in the striatum by cocaine J Neurosci 13, 423–433PubMedGoogle Scholar
  7. 7.
    Beretta, S., Robertson, H. A., and Graybiel, A M. (1993) Neurochemically specialized projection neurons of the striatum respond differently to psychomotor stimulants Prog Brain Res 99, 201–205CrossRefGoogle Scholar
  8. 8.
    Nestler, E J., Hope, B T., and Widnell, K L. (1993) Drug addiction’ a model for the molecular basis of neural plasticity. Neuron 11, 995–1006PubMedCrossRefGoogle Scholar
  9. 9.
    Dragunow, M. and Robertson, H. A (1987) Kindling stimulation induces c-fos protein(s) in granule cells of the rat dentate gyrus Nature 329, 441, 442.PubMedCrossRefGoogle Scholar
  10. 10.
    Dragunow, M., Robertson, H A., and Robertson, G. S (1988) Effects of kindled seizures on the induction of c-fos protein(s) in mammalian neurons. Exp Neurol. 102, 261–263.PubMedCrossRefGoogle Scholar
  11. 11.
    Chiasson, B J, Dennison, Z., and Robertson, H. A. (1995) Amygdala kindling and immediate-early genes Mol Brain Res 29, 19l–l99.CrossRefGoogle Scholar
  12. 12.
    Sinomato, M., Hosford, D. A, Labiner, D. M., Shin, C., Mansbach, H H., and McNamara, J. O. (1991) Differential expression of immediate early genes in the hippocampus in the kindling model of epilepsy Mol Brain Res 11, 115–124.CrossRefGoogle Scholar
  13. 13.
    Cole, A. J., Saffen, D. W., Baraban, J M., and Worley, P F (1989) Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation. Nature 340, 474–476PubMedCrossRefGoogle Scholar
  14. 14.
    Wisden, W., Errington, M L., Williams, S., Dunnett, S. B., Waters, C., Hitchcock, D., Evan, G., Bliss, T V. P., and Hunt, S. P (1990) Differential expression of immediate-early genes in the hippocampus and spinal cord. Neuron 4, 603–614PubMedCrossRefGoogle Scholar
  15. 15.
    Dragunow, M., Currte, R. W., Faull, R. L. M., Robertson, H. A., and Jansen, K. (1989) Immediate-early genes, kindling and long-term potentiation Neurosci Biobehav. Rev. 13, 301–313PubMedCrossRefGoogle Scholar
  16. 16.
    Robertson, H A (1992) Immediate-early genes, neuronal plasticity, and memory Biochem Cell Biol 70, 729–737PubMedCrossRefGoogle Scholar
  17. 17.
    Rusak, B., Robertson, H A, Wisden, W., and Hunt, S P (1990) Light pulses that shift rhythms induce gene expression in the suprachlasmatic nucleus Science 248, 1237–1240.PubMedCrossRefGoogle Scholar
  18. 18.
    Sheng, M and Greenberg, M E (1990) The regulation and function of c-fos and other immediate-early genes in the nervous system Neuron 4, 477–485PubMedCrossRefGoogle Scholar
  19. 19.
    Robertson, H A and Dragunow, M. (1990) From synapse to genome the role of immediate-early genes in permanent alterations in the central nervous system, in Current Aspects of the Neurosciences (Osborne, N N., eds), Macmillan, London, pp 143–157Google Scholar
  20. 20.
    Sonnenberg, J L., Rauscher, J R., III, Morgan, J I, and Curran, T (1989) Regulation of proenkephalin by Fos and Jun. Science 246, 1622–1625.PubMedCrossRefGoogle Scholar
  21. 21.
    Hengerer, B., Lindholm, D., Heumann, R, Ruther, U., Wagner, E F., and Thoenen, H (1990) Lesion-induced increase in nerve growth factor mRNA is mediated by c-fos Proc Natl Acad Sci USA 87, 3899–3903.PubMedCrossRefGoogle Scholar
  22. 22.
    Routtenberg, A. (1995) Knockout mouse fault 1ines. Nature 374, 314, 315PubMedCrossRefGoogle Scholar
  23. 23.
    Smeyne, R J, Curran, T., and Morgan, J.I (1992) Temporal and spatial expression of a fos-lac Z transgene in the developing nervous system Mol. Brain Res 16, 158–162PubMedCrossRefGoogle Scholar
  24. 24.
    Herms, J., Zurmohle, U., Schlingensiepen, R., Brysch, W., and Schhngensiepen, K H. (1994) Developmental expression of transcription factor zif268 in the rat brain. Neurosci. Lett. 165, 171–174.PubMedCrossRefGoogle Scholar
  25. 25.
    Gray, G E. and Sanes, J. E. (1992) Lineage of radial glia in the chicken optic tectum Development 114, 271–283PubMedGoogle Scholar
  26. 26.
    Glorioso, J C., Goins, W. F., Meaney, C A., Fink, DJ, and De Luca, N. A. (1994) Gene transfer to brain using herpes simplex virus vectors. Ann Neurol 35, S28–S34PubMedCrossRefGoogle Scholar
  27. 27.
    Akli, S., Caillaud, C, Vigne, E., Stratford-Perricaudet, L. D., Poenaru, L., Perricaudet, M., Kahn, A., and Peschanski, M R. (1993) Transfer of a foreign gene into brain using adenovirus vectors. Nature Genet 3, 219–223.CrossRefGoogle Scholar
  28. 28.
    Stein, C. A. and Cohen, J S. (1988) Oligonucleotides as inhibitors of gene expression: a review Cancer Res. 48, 2659–2668.PubMedGoogle Scholar
  29. 29.
    Wagner, R W. (1994) Gene inhibition using antisense oligodeoxynucleotides Nature 372, 333–335PubMedCrossRefGoogle Scholar
  30. 30.
    Wahlestedt, C. (1994) Antisense oligonucleotide strategies in neuropharmacology. Trends Pharmacol Sci 15, 42–46PubMedCrossRefGoogle Scholar
  31. 31.
    Chiasson, B J., Hooper, M. L., Murphy, P R., and Robertson, H A (1992) Antisense oligonucleotide eliminates in vivo expression of c-fos in mammalian brain Eur J Pharmacol Mol Pharmacol 227, 451–453CrossRefGoogle Scholar
  32. 32.
    Chiasson, B. J., Hooper, M. L., and Robertson, H A (1992) Amphetamine induced rotational behavior in non-lesioned rats: a role for c-fos expression in the striatum. Soc Neurosci Abst 18, 562Google Scholar
  33. 33.
    Hooper, M L., Chiasson, B. J., and Robertson, H A. (1994) Infusion into the brain of an antisense oligonucleotide to the immediate-early gene c-fos suppresses production of Fos and produces a behavioral effect Neuroscience 63, 917–924.PubMedCrossRefGoogle Scholar
  34. 34.
    Ungerstedt, U (1971) Striatal doparnine release after amphetamine or nerve degeneration revealed by rotational behaviour Acta Physiol. Scand Suppl 367, 49–68PubMedGoogle Scholar
  35. 35.
    Robertson, G. S. and Robertson, H. A. (1987) Dl and D2 dopamine agonist synergism. separate sites of action. Trends Pharmacol Sci 8, 295–299.CrossRefGoogle Scholar
  36. 36.
    Robertson, G. S. and Robertson, H. A. (1989) Evidence that L-dopa-induced rotational behavior is dependent on both striatal and nigral mechanisms J Neurosci 9, 3326–3331.PubMedGoogle Scholar
  37. 37.
    Paul, M L., Graybiel, A M., David, J-C., and Robertson, H A (1992) D1-like and D2-like dopamine receptors synergistically activate rotation and c-fos expression in the dopamine-depleted striatum in a rat model of Parkinson’s disease. J Neurosci 12, 3729–3742PubMedGoogle Scholar
  38. 38.
    Robertson, H A (1992) Dopamine receptor interactions’ some implications for the treatment of Parkinson’s disease. Trends Neurosci 15, 20l–206CrossRefGoogle Scholar
  39. 39.
    Robertson, H A., Peterson, M. R, Murphy, K., and Robertson, G. S. (1989) D1-dopamine receptor agonists selectively activate striatal c-fos independent of rotational behaviour. Brain Res 503, 346–349.PubMedCrossRefGoogle Scholar
  40. 40.
    Robertson, G S., Herrera, D. G., Dragunow, M., and Robertson, H A. (1989) L-Dopa activates c-fos expression in the striatum of 6-hydroxydopamine-lesioned rats Eur J Pharmacol 159, 99, 100PubMedCrossRefGoogle Scholar
  41. 41.
    Robertson, G S., Vincent, S R., and Fibiger, H C (1992) Dl and D2 dopamine receptors differentially regulate c-fos expression in striatonigral and striatopallidal neurons Neuroscience 49, 285–296PubMedCrossRefGoogle Scholar
  42. 42.
    Merchant, K. M. and Miller, M A (1994)Coexpressionof neurotensin and c-fos mRNAs in rat neostriatal neurons following acute haloperidol Brain Res Mol Brain Res 23, 271–277PubMedCrossRefGoogle Scholar
  43. 43.
    Dragunow, M., Lawlor, P A., Chiasson, B. J., and Robertson, H A (1993) Antisense to c-fos suppresses both Fos and Jun B expression in rat striatum and generates apomorphine-and amphetamine-induced rotation. Neuroreport 5, 305, 306PubMedCrossRefGoogle Scholar
  44. 44.
    Sommer, W., Bjelke, B., Ganten, D., and Fuxe, K. (1993) Antisense oligonucleotide to c-fos induces ipsilateral rotational behavior to d-amphetarnine Neuroreport 5, 277–280PubMedCrossRefGoogle Scholar
  45. 45.
    Merchant, K M. (1994) c-fos antisense oligonucleotide specifically attenuates haloperidolinduced increases in neurotensin/neuromedin N mRNA expression in rat dorsal striatum. Mol Cell Neuroscience 5, 336–344.CrossRefGoogle Scholar
  46. 46.
    Heilig, M., Engel, J A., and Soderpalm, B (1993) c-fos antisense in the nucleus accumbens blocks the locomotor stimulant action of cocaine. Eur. J. Pharmacol 236, 339, 340.PubMedCrossRefGoogle Scholar
  47. 47.
    Robertson, G. S., Tetzlaff, W., Bedard, A, St-Jean, M., and Wigle, N. (1995) c-fos mediates antipsychotic-induced neurotensin gene expression in the rodent striatum Neuroscience 67, 325–344PubMedCrossRefGoogle Scholar
  48. 48.
    Gillardon, F., Beck, H., Uhlmann, E., Herdegen, T., Sandkuler, J., Peyman, A., and Zimmermann, M. (1994) Inhibition of c-fos protein expression in rat spinal cord by antisense oligodeoxynucleotide superfusion Eur J Neurosci. 6, 880–884PubMedCrossRefGoogle Scholar
  49. 49.
    Chiang, M-Y., Chan, H., Zounes, M. A., Freier, S M., Lima, W F., and Bennett, C. F (1991) Antisense oligonucleotides inhibit intercellular adhesion molecule 1 expression by two distinct mechanisms. J Biol Chem 266, 18,162–l8,171PubMedGoogle Scholar
  50. 50.
    Carter, G. and Lemoine, N. R (1993) Antisense technology for cancer therapy does it make sense? Br J Cancer 67, 869–876.PubMedCrossRefGoogle Scholar
  51. 51.
    Woolf, T M, Jennings, G B., Rebagliati, M, and Melton, D. A (1990) The stability, toxicity and effectiveness of unmodified and phosphorothioate antisense oligodeoxynucleotides in Xenopus oocytes and embryos Nucleic Acids Res 18, 1763–1769PubMedCrossRefGoogle Scholar
  52. 52.
    Krieg, A M (1993) Uptake and efficacy of phosphodiester and modified antisense oligonucleotides in primary cell cultures Clin Chem 39, 710–712Google Scholar
  53. 53.
    Wahlestedt, C., Golanov, E., Yamamoto, S., Yee, F., Ericson, H., Yoo, H., Inturrisi, C E., and Reis, D. J (1993) Antisense oligonucleotides to NMDA-Rl receptor channel protect cortical neurons from excitotoxicity and reduce focal ischaemic infarctions. Nature 363, 260–263PubMedCrossRefGoogle Scholar
  54. 54.
    Wahlestedt, C., Pich, E M., Koob, G. F., Yee, F., and Heilig, M. (1993) Modula-tion of anxiety and neuropeptide Y-Y1 receptors by antisense oligodeoxynucleotides Science 259, 528–531PubMedCrossRefGoogle Scholar
  55. 55.
    Paul, M L., Currie, R W., and Robertson, H A (1995) Priming of a Dl dopamine receptor behavioural response is dissociated from striatal immediate-early gene activity Neuroscrence 66, 347–359CrossRefGoogle Scholar
  56. 56.
    Teskey, C G., Atkinson, B. G., and Cain, D P (1991) Expression of the proto-oncogene c-fos following electrical kindling in the rat Mol Brain Res 11, 1–10.PubMedCrossRefGoogle Scholar
  57. 57.
    Naranjo, J. R., Mellstrom, B., Achaval, M., and Sassone-Corsi, P. (1991) Molecular pathways of pain: fos/jun-mediated activation of noncanonical AP-1 site in the prodynorphin gene Neuron 6, 606.CrossRefGoogle Scholar
  58. 58.
    Rossier, J (1993) Biosynthesis of enkephalm-derived peptides, in Handbook of Experimental Pharmacology Oplords I (Herz, A., ed.), Springer-Verlag, Germany, pp. 423–447Google Scholar
  59. 59.
    Hollt, V (1993) Regulation of opioid peptide gene expression, in Handbook of Experimental Pharmacology Oprolds I (Herz, A., ed.), Springer-Verlag, Germany, pp. 307–346.Google Scholar
  60. 60.
    Konradi, C., Kobierski, L A., Nguyen, T. V., Heckers, S., and Hyman, S. E (1993) The c-AMP-response-element-binding-protein interacts but Fos protein does not interact, with the proenkephalin enhancer in rat stnatum Proc Natl Acad Sci USA 90, 7005–7009PubMedCrossRefGoogle Scholar
  61. 61.
    Goddard, G. V., McIntyre, D., and Leech, C. (1969) A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol 25, 295–330PubMedCrossRefGoogle Scholar
  62. 62.
    Racine, R. J. (1972) Modification of seizure activity by electrical stimulation motor seizure Electroencephalogr Clin Neurophysiol 38, 28l–294Google Scholar
  63. 63.
    Cain, D. P. (1993) Kindling and the amygdala, in The Amygdala Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction (Aggleton, J. P., ed.), Wiley-Liss, New York, pp. 539–560.Google Scholar
  64. 64.
    Downs, A W and Eddy, N B. (1932) The effect of repeated doses of cocaine on the rat. J Pharmacol Exp Therap 46, 199, 200.Google Scholar
  65. 65.
    Shin, C., McNamara, J O., Morgan, J I, Curran, T., and Cohen, D R (1990) Induction of c-fos mRNA expression by afterdischarge in the hippocampus of naive and kindled rats J Neurochem 55, 1050–1055PubMedCrossRefGoogle Scholar
  66. 66.
    Labiner, D M., Butler, L S., Cao, Z., Hosford, D. A., Shin, C., and McNamara, J O (1993) Induction of c-fos mRNA by kindled seizures: complex relationship with neuronal burst firing. J Neurosci 13, 744–751.PubMedGoogle Scholar
  67. 67.
    Chiasson, B. J., Armstrong, J N., Hooper, M L., Murphy, P R., and Robertson, H A. (1994) The application of antisense oligonucleotide technology to the brain some pitfalls Cell Mol Neurobiol 14, 507–521PubMedCrossRefGoogle Scholar
  68. 68.
    Zhang, M. and Creese, I (1993) Antisense oligonucleotide reduces brain dopamine D2 receptor behavioral correlates. Neurosci. Lett 161, 223–226.PubMedCrossRefGoogle Scholar
  69. 69.
    Zhou, L. M., Zhang, S P, Qin, Z H., and Weiss, B. (1994) In vivo administration of an oligonucleotide antisense to the D2 dopamine receptor messenger RNA inhibits D2 dopamine receptor mediated behavior and the expression of D2 dopamine receptors in mouse striatum. J. Pharmacol Exp Ther 268, 1015–1023PubMedGoogle Scholar
  70. 70.
    Guvakova, M. A., Yakubov, L A., Vlodavsky, I, Tonkmson, J L., and Stem, C A. (1995) Phosphorothioate ohgodeoxynucleotides bind to basic fibroblast growth factor, inhibit its binding to cell surface receptors, and remove it from low affinity binding sites on extracellular matrix J Biol Chem 270, 2620–2627PubMedCrossRefGoogle Scholar
  71. 71.
    Perez, J R., Li, Y., Stem, C. A., Majumder, S., van Oorschot, A., and Narayanan, R (1994) Sequence-independent induction of Sp1 transcription factor activity by phosphorothioate oligonucleotides. Proc Natl Acad Sei USA 91, 5957–5961CrossRefGoogle Scholar
  72. 72.
    Hong, M., Chiasson, B J., Murphy, K. M. A., and Robertson, H. A. (1995) Effects of thio end-capped oligonucleotides on rat striatal c-fos expression and behaviour following amphetamine challenge. International Sympostum on the Regulation of Gene Expression. Practical Approaches Oxford, UK, March 26–28Google Scholar
  73. 73.
    Chiasson, B J, Hong, M., Armstrong, J. N., and Robertson, H. A. (1995) Comparative effects of fully thio substituted and end-capped oligonucleotides directed at c-fos in amygdala kindling. International Symposium on the Regulation of Gene Expression. Practical Approaches, Oxford, UK, March 26–28Google Scholar
  74. 74.
    Standifer, K. M., Chten, C-C., Wahlestedt, C., Brown, G. P., and Pastemak, G. W. (1994) Selective loss of delta opioid analgesia and binding by antisense oligo-deoxynucleotides to a delta opioid receptor. Neuron 12, 805–810PubMedCrossRefGoogle Scholar
  75. 75.
    Crooke, S T. (1995) Progress in antisense technology. International Symposium on the Regulation of Gene Expression: Practical Approaches. Oxford, UK, March 26–28.Google Scholar
  76. 76.
    Stein, C. A. and Cheng, Y-C (1993) Antisense oligonucleotides as therapeutic agents-is the bullet really magical? Science 261, 1004–1012PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 1996

Authors and Affiliations

  • Bernard J. Chiasson
    • 1
  • Murray Hong
    • 1
  • Michele L. Hooper
    • 1
  • John N. Armstrong
    • 1
  • Paul R. Murphy
    • 2
  • Harold A. Robertson
    • 1
  1. 1.Department of Pharmacology, Laboratory of Molecular Neurobiology, Faculty of MedicineDalhousie UniversityHalifaxCanada
  2. 2.Department of Physiology and Biophysics, Laboratory of Molecular Neurobiology, Faculty of MedicineDalhousie UniversityHalifaxCanada

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