CRITICAL TOPICS FORUM
What is the Meaning of the ATP Surge During Sleep?
DOI: 10.5665/SLEEP.1102
Commentary on Dworak et al. Sleep and brain energy levels: ATP changes during sleep. Journal of Neuroscience 2010;30:9007-16.
Margaret Wong-Riley, PhD
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI
The recent paper by Dworak et al.1 reported a surprising finding, that there was a “surge in ATP levels” in the initial hours
of spontaneous sleep in several brain regions, that the “surge”
was prevented or delayed by sleep deprivation, and that an inverse relationship existed in diurnal fluctuations between ATP
and P-AMPK levels. The authors hypothesized that “sleep is
for an energy surge” permitting “energy-consuming anabolic
processes, such as protein and fatty acid synthesis, to occur.”
The necessity for sleep is universally accepted. Sleep deprivation, especially when prolonged, can lead to dire multisystem dysfunctions, even death.2 The lingering question has
been, “What feature(s) of sleep is(are) necessary for health and
for life?” Benington and Heller’s3 proposal that sleep is for the
restoration of brain energy metabolism is attractive, and their
focus was on astrocytic glycogen store for the replenishment
of energy. Dworak et al. challenged the concept of restoration
and proposed that the sleep-induced ATP “surge” is the key for
anabolic processes.
The first question that comes to mind with the spike in ATP
level is, “Does this reflect an increase in ATP synthesis, a decrease in ATP degradation, and/or a decrease in ATP usage?”
This is central to the argument of a “purpose,” if there is one,
for such a “surge.” If the surge is dependent on ATP synthesis
and is necessary for anabolic functions, then one has to ask,
“Is there a difference in protein synthesis between awake and
asleep?” and “Does anabolic activity require ATP levels that
far outweigh the ATP needs of other functions?” To the first
question, the extensive study on 57 brain regions of monkeys
showed no statistically significant difference in protein synthesis rates between awake and asleep states (although a significantly higher rate was found during deep sleep versus light
sleep).4 In the rat suprachiasmatic nucleus with an endogenous
circadian pacemaker, no evidence in circadian rhythm of protein synthesis was detected.5 The screening of 10,000 genes in
rats revealed that most genes were up-regulated in wakefulness
and sleep deprivation as compared to sleep, and not vice versa.6
However, even if protein synthesis rates were higher during
sleep than wakefulness, it leads naturally to the second question
posed above. The answer, based on the published data thus far,
supports the conclusion that protein synthesis consumes relatively little energy.7,8 In the rabbit retina or the rat brain, protein
synthesis accounts for only 1.3-2% of total energy consumption,8,9 and phospholipid turnover consumes only ~5%.9 By all
accounts, the bulk of energy consumed by neurons is for the
active transport of ions against their concentration and electrical gradients in relationship to neuronal activity, i.e., the more
frequently a neuron’s membranes are depolarized by excitatory
input, the greater its energy demand for repolarization.9,10 Much
of this energy is consumed by dendrites, the major receptive
sites for excitatory synapses.10
If anabolic activities are not likely to be the major reason
for increased ATP synthesis (and this can be further tested with
protein synthesis inhibitors), then what, if any, function(s)
during sleep would require such a surge? In rats, both NREM
and REM occur in both the light and dark cycles, and bouts
of wakefulness exist in the light cycle.11 If the surge of ATP
is related to NREM activity, as Dworak et al. suggested, then
shouldn’t there be a similar “surge” around the 7th-8th hour of
the dark cycle, when there is much NREM activity (see Figures
1 and 711)? If brain metabolic activities during wakefulness and
REM are greater than those during NREM,12,13 then the relatively low ATP levels (compared to the “surge”) should reflect
greater ATP usage during the waking period that consumes the
energy generated. In neurons, energy is not generated unless energy is used.14 So, the ATP “surge” is not likely to be increased
ATP synthesis, as the need and usage are reduced during this
time. That leaves a decrease in ATP degradation with an accumulation of unused ATP as another plausible explanation for
the “surge.” This is consistent with authors’ findings of a delay
or prevention of “surge” when the animals were sleep-deprived,
i.e., when their energy consumption was increased. A high level
of ATP is inhibitory to cytochrome c oxidase,15 a terminal enzyme of the mitochondrial electron transport chain. Such inhibition limits further energy generation, with a possible benefit
of preventing excessive accumulation of reactive oxygen species, a byproduct of energy metabolism.
Dworak et al.’s findings are indeed intriguing and provocative. However, the rationale for the ATP “surge,” at least for this
reader, deserves further probing.
DISCLOSURE STATEMENT
Dr. Wong-Riley has indicated no financial conflicts of interest.
REFERENCES
1. Dworak M, McCarley RW, Kim T, Kalinchuk AV, Basheer R. Sleep
and brain energy levels: ATP changes during sleep. J Neurosci
2010;30:9007-16.
2. Rechtschaffen A, Bergmann BM, Everson CA, Kushida CA, Gilliland
MA. Sleep deprivation in the rat: X. Integration and discussion of the
findings. Sleep 1989;12:68-87.
Submitted for publication April, 2011
Accepted for publication April, 2011
Address correspondence to: Margaret Wong-Riley, PhD, Department of
Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin,
8701 Watertown Plank Road, Milwaukee, WI 53226; Tel: (414) 955-8467;
Fax: (414) 955-6517; E-mail: [email protected]
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