title: Endogenous rhythmicity of Bmal1 and Rev-erb alpha in the hamster pineal gland is not driven by norepinephrine.
abstract: Pineal melatonin is synthesized with daily and seasonal rhythms following the hypothalamic clock-driven release of norepinephrine (NE). The pineal gland of rats and mice, like the biological clock, expresses a number of clock genes. However, the role of pineal clock elements in pineal physiology is still unknown. We examined the expression and regulation of several clock genes (Per1, Cry2, Bmal1 and Rev-erb alpha) under different lighting conditions or following adrenergic treatments in the Syrian hamster, a seasonal rodent. We found that Per1 and Cry2 genes were similarly regulated by the nocturnal release of NE: levels of Per1 and Cry2 mRNA displayed a nocturnal increase that was maintained after 2 days in constant darkness (DD) but abolished after 2 days under constant light (LL), a condition that suppresses endogenous NE release, or after an early night administration of the adrenergic antagonist propranolol. In contrast, Bmal1 and Rev-erb alpha exhibited a different pattern of expression and regulation. mRNA levels of both clock genes displayed a marked daily variation, maintained in DD, with higher values at midday for Bmal1 and at day/night transition for Rev-erb alpha. Remarkably, the daily variation of both Bmal1 and Rev-erb alpha mRNA was maintained in LL conditions and was not affected by propranolol. This study confirms the daily regulation of Per1 and Cry2 gene expression by NE in the pineal gland of rodents and shows for the first time that a second set of clock genes, Bmal1 and Rev-erb alpha are expressed with a circadian rhythm independent of the hypothalamic clock-driven noradrenergic signal.
authors.affiliation: Département de Neurobiologie des Rythmes, Institut des Neurosciences Cellulaires et Intégratives, UPR CNRS 3212, Université de Strasbourg, 5 rue Blaise Pascal, 67084 Strasbourg Cedex, France.
authors.forename: Prapimpun
authors.initials: P
authors.lastname: Wongchitrat
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Felder-Schmittbuhl
authors.forename: Pansiri
authors.initials: P
authors.lastname: Phansuwan-Pujito
authors.forename: Paul
authors.initials: P
authors.lastname: Pévet
authors.forename: Valérie
authors.initials: V
authors.lastname: Simonneaux
mesh_terms: D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001683:Biological Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D006224:Cricetinae; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D008647:Mesocricetus; D009638:Norepinephrine / Q000378:metabolism*; D010870:Pineal Gland / Q000378:metabolism*
chemical_list: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D009638:Norepinephrine; C538961:Bmal1 protein, mouse