The energy hypothesis of sleep revisited

Scharf, Matthew T.; Naidoo, Nirinjini; Zimmerman, John E.; Pack, Allan I.

doi:10.1016/j.pneurobio.2008.08.003

Cited by 165 publications

(111 citation statements)

References 174 publications

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“…11,21,45,52,53 Extracellular adenosine is derived in part from intracellular adenosine via equilibrative adenosine transporters. Adenosine is also secreted through regulated vesicular exocytosis.…”

Section: Introductionmentioning

confidence: 99%

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

Varshavsky

2012

Protein Science

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Despite extensive understanding of sleep regulation, the molecular-level cause and function of sleep are unknown. I suggest that they originate in individual neurons and stem from increased production of protein fragments during wakefulness. These fragments are transient parts of protein complexes in which the fragments were generated. Neuronal Ca 21 fluxes are higher during wakefulness than during sleep. Subunits of transmembrane channels and other proteins are cleaved by Ca 21 -activated calpains and by other nonprocessive proteases, including caspases and secretases. In the proposed concept, termed the fragment generation (FG) hypothesis, sleep is a state during which the production of fragments is decreased (owing to lower Ca 21 transients) while fragment-destroying pathways are upregulated. These changes facilitate the elimination of fragments and the remodeling of protein complexes in which the fragments resided. The FG hypothesis posits that a proteolytic cleavage, which produces two fragments, can have both deleterious effects and fitness-increasing functions. This (previously not considered) dichotomy can explain both the conservation of cleavage sites in proteins and the evolutionary persistence of sleep, because sleep would counteract deleterious aspects of protein fragments. The FG hypothesis leads to new explanations of sleep phenomena, including a longer sleep after sleep deprivation. Studies in the 1970s showed that ethanol-induced sleep in mice can be strikingly prolonged by intracerebroventricular injections of either Ca 21 alone or Ca 21 and its ionophore (Erickson et al., Science 1978;199:1219-1221 Harris, Pharmacol Biochem Behav 1979;10:527-534; Erickson et al., Pharmacol Biochem Behav 1980;12:651-656). These results, which were never interpreted in connection to protein fragments or the function of sleep, may be accounted for by the FG hypothesis about molecular causation of sleep.

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Section: Introductionmentioning

confidence: 99%

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

Varshavsky

2012

Protein Science

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“…The physiological cause is unclear, but the brain does store a small but significant quantity of glycogen (27), which presumably is used in response to acute neuroglycopenia. Sleep deprivation leads to depletion of cerebral glycogen (28,29), and an important restorative function of sleep may be to replenish stores of this substrate (9,29,30). This effect on neuroglycopenic symptoms may have been exacerbated by depletion of neuronal glycogen reserves associated with sleep deprivation.…”

Section: Discussionmentioning

confidence: 99%

“…Sleep deprivation and hypoglycemia may share a final common pathway to influence the depletion of cerebral glucose (9). Adults with type 1 diabetes may experience these conditions concomitantly in everyday life, particularly if they are involved in shift work, and little is known about the effect of this dual insult on cognitive function.…”

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confidence: 99%

Effects of Sleep Deprivation on Hypoglycemia-Induced Cognitive Impairment and Recovery in Adults With Type 1 Diabetes

et al. 2016

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OBJECTIVETo ascertain whether hypoglycemia in association with sleep deprivation causes greater cognitive dysfunction than hypoglycemia alone and protracts cognitive recovery after normoglycemia is restored. RESEARCH DESIGN AND METHODSFourteen adults with type 1 diabetes underwent a hyperinsulinemic, hypoglycemic clamp on two separate occasions. Before one glucose clamp, the participants stayed awake overnight to induce sleep deprivation. Participants were randomized and counterbalanced to the experimental condition. Cognitive function tests were performed before and during hypoglycemia and for 90 min after restoration of normoglycemia. RESULTSCognitive impairment during hypoglycemia did not differ significantly between the sleep-deprived and non-sleep-deprived conditions. However, in the sleepdeprived state, digit symbol substitution scores and choice reaction times were significantly poorer during recovery (P < 0.001) and hypoglycemia symptom scores were significantly higher (P < 0.001), even when symptoms that may have been caused by sleep deprivation, such as tiredness, were removed. CONCLUSIONSHypoglycemia per se produced a significant decrement in cognitive function; coexisting sleep deprivation did not have an additive effect. However, after restoration of normoglycemia, preceding sleep deprivation was associated with persistence of hypoglycemic symptoms and greater and more prolonged cognitive dysfunction during the recovery period.

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“…Use of natural sleep (Almli et al 2007;Nordahl et al 2008) and mock scanners (Rosenberg et al 1997) have been heralded as fostering scanning success without pharmacologic intervention (Raschle et al 2009;Nordahl et al 2008). However, sleep or sedation may still alter functional and energetic characteristics of the brain (germane to fMRI, 31 P-MRS) (Scharf et al 2008;Dworak et al 2010), and energetic assessments may benefit from muscle exercise/ recovery testing that necessarily requires non-sleeping, nonsedated subjects. Sedation and separate mock scanner visits raise costs (Vanderby et al 2010) and increase the time burden on families.…”

Section: Introductionmentioning

confidence: 99%

Erratum to: Brief Report: Approaches to 31P-MRS in Awake, Non-Sedated Children With and Without Autism Spectrum Disorder

Erickson¹,

Zeeland²,

Hamilton³

et al. 2013

J Autism Dev Disord

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We piloted a suite of approaches aimed to facilitate a successful series of up to four brain and muscle 31 phosphorus-magnetic resonance spectroscopy scans performed in one session in 12 awake, non-sedated subjects (ages 6-18), 6 with autism spectrum disorders (ASD) and 6 controls. We targeted advance preparation, parental input, physical comfort, short scan protocols, allocation of extra time, and subject emotional support. One hundred percent of subjects completed at least one brain scan and one leg muscle scan: 42 of 46 attempted scans were completed (91 %), with failures dominated by exercise muscle scans (completed in 6/6 controls but 3/6 cases). One completed scan lacked usable data unrelated to subject/scan procedure (orthodonture affected a frontal brain scan). As a group, these methods provide a foundation for conduct and enhancement of future MR studies in pediatric subjects with ASD.

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The energy hypothesis of sleep revisited

Cited by 165 publications

References 174 publications

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

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

Effects of Sleep Deprivation on Hypoglycemia-Induced Cognitive Impairment and Recovery in Adults With Type 1 Diabetes

Erratum to: Brief Report: Approaches to 31P-MRS in Awake, Non-Sedated Children With and Without Autism Spectrum Disorder

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