We investigated the role of brain ketone body metabolism in brain functions including sleep regulations. Chronic sleep disruption decreased sleep amount and attenuated sleep depth, accompanying by glucose intolerance in mice. These sleep-disrupted mice showed no change in plasma ketone body concentration, although both central and peripheral injection of ketone bodies enhanced sleep depth. In addition, neuron-specific over expression of ketone body-degrading enzyme induced alteration of sleep rebound after sleep deprivation, anxiety/depression and memory/learning behavior. Central ketone body metabolism may play a significant role in higher brain functions including sleep homeostasis.
