title: Familial circadian rhythm disorder in the diurnal primate, Macaca mulatta.
abstract: In view of the inverse temporal relationship of central clock activity to physiological or behavioral outputs in diurnal and nocturnal species, understanding the mechanisms and physiological consequences of circadian disorders in humans would benefit from studies in a diurnal animal model, phylogenetically close to humans. Here we report the discovery of the first intrinsic circadian disorder in a family of diurnal non-human primates, the rhesus monkey. The disorder is characterized by a combination of delayed sleep phase, relative to light-dark cycle, mutual desynchrony of intrinsic rhythms of activity, food intake and cognitive performance, enhanced nighttime feeding or, in the extreme case, intrinsic asynchrony. The phenotype is associated with normal length of intrinsic circadian period and requires an intact central clock, as demonstrated by an SCN lesion. Entrainment to different photoperiods or melatonin administration does not eliminate internal desynchrony, though melatonin can temporarily reinstate intrinsic activity rhythms in the animal with intrinsic asynchrony. Entrainment to restricted feeding is highly effective in animals with intrinsic or SCN lesion-induced asynchrony. The large isolated family of rhesus macaques harboring the disorder provides a powerful new tool for translational research of regulatory circuits underlying circadian disorders and their effective treatment.
authors.affiliation: Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts, United States of America. zhdanova@bu.edu
authors.forename: Irina V
authors.initials: IV
authors.lastname: Zhdanova
authors.forename: Ken
authors.initials: K
authors.lastname: Masuda
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Bozhokin
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Rosene
authors.forename: Janis
authors.initials: J
authors.lastname: González-Martínez
authors.forename: Steven
authors.initials: S
authors.lastname: Schettler
authors.forename: Eric
authors.initials: E
authors.lastname: Samorodnitsky
mesh_terms: D000818:Animals; D021081:Chronobiology Disorders / Q000188:drug therapy / Q000503:physiopathology*; D002940:Circadian Rhythm; D004569:Electroencephalography; D005247:Feeding Behavior; D008253:Macaca mulatta; D008297:Male; D008550:Melatonin / Q000627:therapeutic use; D010641:Phenotype; D012894:Sleep Stages; D013493:Suprachiasmatic Nucleus / Q000502:physiology
chemical_list: D008550:Melatonin