title: Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation.
abstract: The Intracellular levels of nicotinamide adenine dinucleotide (NAD(+)) are rhythmic and controlled by the circadian clock. However, whether NAD(+) oscillation in turn contributes to circadian physiology is not fully understood. To address this question we analyzed mice mutated for the NAD(+) hydrolase CD38. We found that rhythmicity of NAD(+) was altered in the CD38-deficient mice. The high, chronic levels of NAD(+) results in several anomalies in circadian behavior and metabolism. CD38-null mice display a shortened period length of locomotor activity and alteration in the rest-activity rhythm. Several clock genes and, interestingly, genes involved in amino acid metabolism were deregulated in CD38-null livers. Metabolomic analysis identified alterations in the circadian levels of several amino acids, specifically tryptophan levels were reduced in the CD38-null mice at a circadian time paralleling with elevated NAD(+) levels. Thus, CD38 contributes to behavioral and metabolic circadian rhythms and altered NAD(+) levels influence the circadian clock.
authors.affiliation: Department of Pharmacology, University of California, Irvine, 92697, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Sahar
authors.forename: Veronica
authors.initials: V
authors.lastname: Nin
authors.forename: Maria Thereza
authors.initials: MT
authors.lastname: Barbosa
authors.forename: Eduardo Nunes
authors.initials: EN
authors.lastname: Chini
authors.forename: Paolo
authors.initials: P
authors.lastname: Sassone-Corsi
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D008099:Liver; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009154:Mutation; D009243:NAD / Q000378:metabolism*; D012146:Rest / Q000502:physiology
chemical_list: D008562:Membrane Glycoproteins; D009243:NAD; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1