Effects of Dietary Resveratrol on the Sleep-Wake Cycle in the Non-Human Primate Gray Mouse Lemur (Microcebus murinus)*

Abstract

Converging evidence shows that the non-human primate gray mouse lemur (Microcebus murinus) is ideal for the study of the aging process and for testing the effects of new therapies and dietary interventions on age-associated pathologies. One such dietary supplement is resveratrol (RSV), a dietary polyphenolic compound with several positive effects on metabolic functions and longevity. However, little is known about the effect of RSV on the lemur sleep-wake cycle, which reflects mammalian brain function and health. In the present study, the authors investigated this effect by comparing sleep-wake cycles in adult lemurs based on electroencephalographic (EEG) rhythms. The effect of short-term RSV supplementation on the sleep-wake cycle of mouse lemurs was evaluated in entrained conditions (long-day photoperiods, light:dark 14:10). After 3 wks of RSV supplementation, the animals exhibited a significantly increased proportion of active-wake time, occurring mainly during the resting phase of the sleep-wake cycle (+163%). The increase in active-wake time with RSV supplementation was accompanied by a significant reduction of both paradoxical sleep (−95%) and slow-wave sleep (−38%). These changes mainly occurred during the resting phase of the sleep-wake cycle (RSV supplementation induced negligible changes in active-wake time during the active phase of the sleep-wake cycle). The present data suggest that RSV may be a potent regulator of sleep-wake rhythms and could be of major interest in the study of sleep perturbations associated with aging and neuropathology. (Author correspondence: [email protected])

Keywords:

• Circadian rhythms
• Electroencephalography
• Metabolism
• Microcebus murinus
• Resveratrol
• Sleep

ACKNOWLEDGMENTS

The research leading to the present results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) for the Innovative Medicine Initiative under grant agreement no. 115009 (“Prediction of Cognitive Properties of New Drug Candidates for Neurodegenerative Diseases in Early Clinical Development,” Pharmacog) for the study of electroencephalographic (EEG) rhythms in lemurs during the sleep-wake cycle. For further information on the PharmaCog project, please refer to www.alzheimer-europe.org.

Recognition is due to Dr. Marina Bentivoglio, Dr. Giuseppe Bertini, Dr. Paolo Fabene, and Dr. Philippe Lestaevel for their help in EEG/EMG recording methods and sleep scoring. Special recognition is also due to Dr. Marina Bentivoglio for her help in proofreading and improving the manuscript. The authors acknowledge the participation in this project of Dr. Martine Perret, director of the laboratory of Mécanismes Adaptatifs et Evolution, UMR 7179, Centre National de la Recherche Scientifique/Muséum National d'Histoire Naturelle, Brunoy, France.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.