Block of c-Fos and JunB expression by antisense oligonucleotides inhibits light-induced phase shifts of the mammalian circadian clock

Eur J Neurosci. 1995 Mar 1;7(3):388-93. doi: 10.1111/j.1460-9568.1995.tb00334.x.


Light-induced phase shifts of circadian rhythmic locomotor activity are associated with the expression of c-Jun, JunB, c-Fos and FosB transcription factors in the rat suprachiasmatic nucleus, as shown in the present study. In order to explore the importance of c-Fos and JunB, the predominantly expressed AP-1 proteins for the phase-shifting effects of light, we blocked the expression of c-Fos and JunB in the suprachiasmatic nucleus of male rats, housed under constant darkness, by intracerebroventricular application of 2 microliters of 1 mM antisense phosphorothioate oligodeoxynucleotides (ASO) specifically directed against c-fos and junB mRNA. A light pulse (300 lux for 1 h) at circadian time 15 induced a significant phase shift (by 125 +/- 15 min) of the circadian locomotor activity rhythm, whereas application of ASO 6 h before the light pulse completely prevented this phase shift. Application of control nonsense oligodeoxynucleotides had no effect. ASO strongly reduced the light-induced expression of c-Fos and JunB proteins. In contrast, light pulses with or without the control nonsense oligodeoxynucleotides evoked strong nuclear c-Fos and JunB immunoreactivity in the rat suprachiasmatic nucleus. These results demonstrate for the first time that inducible transcription factors such as c-Fos and JunB are an essential part of fundamental biological processes in the adult mammalian nervous system, e.g. of light-induced phase shifts of the circadian pacemaker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Circadian Rhythm / physiology*
  • Circadian Rhythm / radiation effects*
  • Injections, Intraventricular
  • Light*
  • Male
  • Molecular Sequence Data
  • Motor Activity / physiology*
  • Motor Activity / radiation effects
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / pharmacology
  • Proto-Oncogene Proteins c-fos / antagonists & inhibitors
  • Proto-Oncogene Proteins c-fos / physiology*
  • Proto-Oncogene Proteins c-jun / antagonists & inhibitors
  • Proto-Oncogene Proteins c-jun / physiology*
  • Rats
  • Suprachiasmatic Nucleus / physiology


  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun