Research Paper Volume 3, Issue 8 pp 794—802
Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation
- 1 Department of Pharmacology, University of California, Irvine, CA 92697, USA
- 2 Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN 55902, USA
- 3 Unite 904 of INSERM (Institut National de la Sante et de la Recherche Medicale) University of California, Irvine, CA 92697, USA
Received: August 26, 2011 Accepted: August 29, 2011 Published: August 31, 2011
https://doi.org/10.18632/aging.100368How to Cite
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.