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

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 expre...

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Main Authors: Wollnik, Franziska (Author) , Brysch, W. (Author) , Uhlmann, E. (Author) , Gillardon, Frank (Author) , Bravo, R. (Author) , Zimmermann, M. (Author) , Schlingensiepen, K. H. (Author) , Herdegen, Thomas (Author)
Format: Article (Journal)
Language:English
Published: March 1995
In: European journal of neuroscience
Year: 1995, Volume: 7, Issue: 3, Pages: 388-393
ISSN:1460-9568
DOI:10.1111/j.1460-9568.1995.tb00334.x
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/j.1460-9568.1995.tb00334.x
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1460-9568.1995.tb00334.x
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Author Notes:F. Wollnik, W. Brysch, E. Uhlmann, F. Gillardon, R. Bravo, M. Zimmermann, K.H. Schlingensiepen, T. Herdegen
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Summary: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 μ1 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 AS0 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.
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Physical Description:Online Resource
ISSN:1460-9568
DOI:10.1111/j.1460-9568.1995.tb00334.x