Photoinducible and rhythmic ICER-CREM immunoreactivity in the rat suprachiasmatic nucleus.
Several genes expressed in the suprachiasmatic nucleus (SCN) are induced by light and are candidate links in the photic entrainment pathway of the SCN's circadian clock. Since the cAMP response element binding protein (CREB) and CRE-mediated gene transcription in the SCN appears to be crucial for light-induced phase shifts of circadian rhythmicity, we analyzed the immunohistochemical expression of proteins encoded by the cAMP response element modulator (CREM) gene, including a repressor isoform (inducible cAMP early repressor [ICER]). ICER-CREM immunoreactivity was detected in cells of the ventrolateral subdivision of the rat SCN after light administration during the subjective night in constant darkness; but only late after light onset (at 240 min), following earlier successive peaks of phosphorylated CREB protein (by 5 min), c-fos mRNA (by 40 min), per 1 mRNA (by 55 min), and c-Fos protein (by 60 min). In constant darkness, there was a modest but significant endogenous rhythm of ICER-CREM immunoreactivity, with a two-fold difference between high levels at circadian time (CT) 10 and low levels at CT 22. Our data raise the possibility that ICER-CREM might be involved in downregulating the SCN expression of immediate-early and "clock" genes after their induction by phase-shifting light pulses.
Schwartz
William J
WJ
Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA. william.schwartz@umassed.edu
Aronin
Neil
N
Sassone-Corsi
Paolo
P
D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count / Q000379:methods; D018797:Cell Cycle Proteins; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008027:Light; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D010507:Periodicity; D017440:Photoperiod; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013493:Suprachiasmatic Nucleus / Q000378:metabolism / Q000528:radiation effects*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C539024:Per1 protein, rat; D056950:Period Circadian Proteins; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D051786:Cyclic AMP Response Element Modulator