title: Altered entrainment to the day/night cycle attenuates the daily rise in circulating corticosterone in the mouse.
abstract: The suprachiasmatic nucleus (SCN) is a circadian oscillator entrained to the day/night cycle via input from the retina. Serotonin (5-HT) afferents to the SCN modulate retinal signals via activation of 5-HT1B receptors, decreasing responsiveness to light. Consequently, 5-HT1B receptor knockout (KO) mice entrain to the day/night cycle with delayed activity onsets. Since circulating corticosterone levels exhibit a robust daily rhythm peaking around activity onset, we asked whether delayed entrainment of activity onsets affects rhythmic corticosterone secretion. Wheel-running activity and plasma corticosterone were monitored in mice housed under several different lighting regimens. Both duration of the light:dark cycle (T cycle) and the duration of light within that cycle was altered. 5-HT1B KO mice that entrained to a 9.5L:13.5D (short day in a T = 23 h) cycle with activity onsets delayed more than 4 h after light offset exhibited a corticosterone rhythm in phase with activity rhythms but reduced 50% in amplitude compared to animals that initiated daily activity <4 h after light offset. Wild type mice in 8L:14D (short day in a T = 22 h) conditions with highly delayed activity onsets also exhibited a 50% reduction in peak plasma corticosterone levels. Exogenous adrenocorticotropin (ACTH) stimulation in animals exhibiting highly delayed entrainment suggested that the endogenous rhythm of adrenal responsiveness to ACTH remained aligned with SCN-driven behavioral activity. Circadian clock gene expression in the adrenal cortex of these same animals suggested that the adrenal circadian clock was also aligned with SCN-driven behavior. Under T cycles <24 h, altered circadian entrainment to short day (winter-like) conditions, manifest as long delays in activity onset after light offset, severely reduces the amplitude of the diurnal rhythm of plasma corticosterone. Such a pronounced reduction in the glucocorticoid rhythm may alter rhythmic gene expression in the central nervous system and in peripheral organs contributing to an array of potential pathophysiologies.
authors.affiliation: Neuroscience Division, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, 80523, United States of America; School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, Nebraska, 68583, United States of America.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Sollars
authors.affiliation: Neuroscience Division, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, 80523, United States of America; Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado, 80309, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Weiser
authors.affiliation: Neuroscience Division, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, 80523, United States of America.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Kudwa
authors.affiliation: Neuroscience Division, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, 80523, United States of America; School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, Nebraska, 68583, United States of America.
authors.forename: Jayne R
authors.initials: JR
authors.lastname: Bramley
authors.affiliation: Neuroscience Division, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, 80523, United States of America; School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, Nebraska, 68583, United States of America.
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Ogilvie
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado, 80309, United States of America.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Spencer
authors.affiliation: Neuroscience Division, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, 80523, United States of America; Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, Arizona, 85004, United States of America.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Handa
authors.affiliation: Neuroscience Division, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, 80523, United States of America; School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, Nebraska, 68583, United States of America.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Pickard
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*
chemical_list: D044302:Receptor, Serotonin, 5-HT1B; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone