title: Serotonin inhibits glutamate- but not PACAP-induced per gene expression in the rat suprachiasmatic nucleus at night.
abstract: Circadian rhythms of physiology and behaviour generated by the brain's biological clock located in the suprachiasmatic nucleus are entrained by light via the retinohypothalamic tract. Two neurotransmitters, glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP), found in this monosynaptic pathway mediate the effects of light to the clock. It is well known that not only light entrains the clock. Nonphotic cues mediated by neurotransmitters such as serotonin reaching the suprachiasmatic nucleus from the midbrain raphe nucleus modulate light-induced phase shifts at night. Two clock genes, per1 and per2, have been attributed a role in light-induced phase shift. In the present study, using an in vitro brain slice model and quantitative in situ hybridization for per1 and per2, we have shown that serotonin induces per1 gene expression at late subjective night but not at early night. Furthermore, serotonin application before glutamate or PACAP blocked glutamate-induced per1 expression at early night and per2 gene expression at late night. In contrast, serotonin did not influence PACAP-induced per gene expression at late night. Triple antigen immunohistochemistry and confocal microscopy supported both a pre- and post-synaptic interaction of retinohypothalamic tract (PACAP-immunoreactive) and serotonin projections on vasoactive intestinal peptide- and gastrin-releasing peptide-containing cell bodies in the ventro-lateral suprachiasmatic nucleus. Our findings suggest that the per genes could be the molecular target for the modulatory effects of serotonin on light signalling to the clock.
authors.affiliation: Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark.
authors.forename: K M
authors.initials: KM
authors.lastname: Sanggaard
authors.forename: J
authors.initials: J
authors.lastname: Hannibal
authors.forename: J
authors.initials: J
authors.lastname: Fahrenkrug
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D003624:Darkness; D019886:Gastrin-Releasing Peptide / Q000378:metabolism; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000008:administration & dosage / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008027:Light; D008297:Male; D018613:Microscopy, Confocal; D009479:Neuropeptides / Q000008:administration & dosage / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D056950:Period Circadian Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*; D014157:Transcription Factors; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: C495403:Adcyap1 protein, rat; D018797:Cell Cycle Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C539024:Per1 protein, rat; C513312:Per2 protein, mouse; C513311:Per2 protein, rat; D056950:Period Circadian Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014157:Transcription Factors; D012701:Serotonin; D014660:Vasoactive Intestinal Peptide; D018698:Glutamic Acid; D019886:Gastrin-Releasing Peptide