title: Homer-1 mRNA in the rat suprachiasmatic nucleus is regulated differentially by the retinohypothalamic tract transmitters pituitary adenylate cyclase activating polypeptide and glutamate at time points where light phase-shifts the endogenous rhythm.
abstract: The suprachiasmatic nucleus (SCN) generates circadian rhythms which are synchronised to the environmental light/dark cycle via the retinohypothalamic tract (RHT). Pituitary adenylate cyclase activating polypeptide (PACAP) and glutamate, two transmitters co-stored in the rat retinohypothalamic tract, are involved in photic entrainment of the circadian pacemaker, but their functional interplay is poorly understood. Homer proteins are involved in glutamatergic receptor function and signalling. By quantitative in situ hybridisation histochemistry we found that light stimulation of rats at early and late night induced Homer-1 gene expression in the SCN at time points where light induces phase-delay or phase-advance, respectively. Using a rat brain slice model Homer-1 mRNA levels in the SCN displayed a modest diurnal variation similar to that in vivo. The changes in Homer-1 gene expression after in vitro stimulation with PACAP and/or glutamate differed at early and late night. Nanomolar PACAP induced Homer-1 gene expression at both early and late night while glutamate was only able to increase Homer-1 mRNA level at early night. PACAP in micromolar concentration had no effect per se, but inhibited the glutamate induced Homer-1 response at early night, while at late night co-administration of PACAP and glutamate mediated a slight induction of Homer-1 gene expression. In conclusion, the RHT transmitters PACAP and glutamate could be responsible for the light-induced expression of Homer-1 in the SCN, and Homer-1 seems to be differentially regulated by the two transmitters at early and late night.
authors.affiliation: Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark.
authors.forename: Henriette S
authors.initials: HS
authors.lastname: Nielsen
authors.forename: Birgitte
authors.initials: B
authors.lastname: Georg
authors.forename: Jens
authors.initials: J
authors.lastname: Hannibal
authors.forename: Jan
authors.initials: J
authors.lastname: Fahrenkrug
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics*; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D000072233:Homer Scaffolding Proteins; D008027:Light; D008297:Male; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D010775:Photic Stimulation; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D014795:Visual Pathways / Q000187:drug effects / Q000378:metabolism*
chemical_list: C495403:Adcyap1 protein, rat; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D018698:Glutamic Acid