Vasoactive intestinal polypeptide induces per1 and per2 gene expression in the rat suprachiasmatic nucleus late at night.
Circadian rhythms in behaviour and physiology generated by the suprachiasmatic nucleus (SCN) are entrained to the environmental light/dark cycle via the retinohypothalamic tract. How light is able to adjust the endogenous rhythm is not fully understood, but induction of the two clock genes per1 and per2 in the SCN is believed to be important for the adjustment. Recently, it was shown that vasoactive intestinal polypeptide (VIP), a neurotransmitter found in light-responsive cells of the SCN, is able to phase shift the circadian rhythm similar to light. In the present study we show by means of an in vitro brain slice model and quantitative in situ hybridization histochemistry that VIP induces both per1 and per2 gene expression in the SCN during late subjective night (CT19). The signalling pathways responsible for the VIP signalling to the clock were investigated using inhibitors of protein kinase A and phospholipase C mediated signalling. Our results demonstrate that both pathways are involved in VIP induced per gene expression and suggest that VIP is important for light-induced phase shift late at night.
Nielsen
Henriette S
HS
Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, DK-2400, Copenhagen NV, Denmark.
Hannibal
Jens
J
Fahrenkrug
Jan
J
D000818:Animals; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics*; D009924:Organ Culture Techniques; D056950:Period Circadian Proteins; D010775:Photic Stimulation; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism* / Q000494:pharmacology
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C539024:Per1 protein, rat; C513312:Per2 protein, mouse; C513311:Per2 protein, rat; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D014660:Vasoactive Intestinal Peptide; D017868:Cyclic AMP-Dependent Protein Kinases; D010738:Type C Phospholipases