Sleep and Brain Energy Levels: ATP Changes during Sleep

Abstract

Sleep is one of the most pervasive biological phenomena, but one whose function remains elusive. Although many theories of function, indirect evidence, and even common sense suggest sleep is needed for an increase in brain energy, brain energy levels have not been directly measured with modern technology. We here report that ATP levels, the energy currency of brain cells, show a surge in the initial hours of spontaneous sleep in wake-active but not in sleep-active brain regions of rat. The surge is dependent on sleep but not time of day, since preventing sleep by gentle handling of rats for 3 or 6 h also prevents the surge in ATP. A significant positive correlation was observed between the surge in ATP and EEG non-rapid eye movement delta activity (0.5-4.5 Hz) during spontaneous sleep. Inducing sleep and delta activity by adenosine infusion into basal forebrain during the normally active dark period also increases ATP. Together, these observations suggest that the surge in ATP occurs when the neuronal activity is reduced, as occurs during sleep. The levels of phosphorylated AMP-activated protein kinase (P-AMPK), well known for its role in cellular energy sensing and regulation, and ATP show reciprocal changes. P-AMPK levels are lower during the sleep-induced ATP surge than during wake or sleep deprivation. Together, these results suggest that sleep-induced surge in ATP and the decrease in P-AMPK levels set the stage for increased anabolic processes during sleep and provide insight into the molecular events leading to the restorative biosynthetic processes occurring during sleep.

Sleep Fragmentation Induces Cognitive Deficits Via Nicotinamide Adenine Dinucleotide Phosphate Oxidase–dependent Pathways in Mouse

“…In addition, we postulate that because the SF-exposed mice exhibited overall preserved sleep architecture, the fact that SF-gp91phox-/Y mice were protected against SF-induced cognitive deficits is highly unlikely to be explained by any underlying disruption of sleep architecture, or by reduced brain energy source bioavailability. This is particularly pertinent when considering the preserved ATP levels and absence of any phosphorylation of AMPK-a (see online supplement), whereas both of these reporters of cellular bioenergetics are markedly altered as a consequence of sleep deprivation (49). Consequently, it is assumed that NADPH-mediated ROS were the major contributor to the disrupted neurobehavioral and cognitive manifestations of SF.…”

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

“…Conversely, the waking brain state can contribute to accumulation of Aβ (Kang et al, 2009), specifically through a higher neurometabolic rate relative to NREM sleep (Buchsbaum et al, 1989). Neurons consume greater levels of oxygen and ATP during wakefulness (Braun et al, 1997; Dworak, McCarley, Kim, Kalinchuk, & Basheer, 2010), while NREM sleep is associated with reduced oxygen consumption and active replenishment of ATP levels (Braun et al, 1997; Dworak et al, 2010). Waking therefore represents a state of higher oxygen, ATP, and glucose consumption, resulting in high rates of metabolic burdens (Everson, Henchen, Szabo, & Hogg, 2014).…”

Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

“…47 In addition, there is no convincing evidence that neuronal energy gains during sleep are significant enough to be functionally relevant (for a recent discussion, see Refs. [48][49][50][51].…”