Changes in brain glycogen after sleep deprivation vary with genotype

Abstract

Sleep has been functionally implicated in brain energy homeostasis in that it could serve to replenish brain energy stores that become depleted while awake. Sleep deprivation (SD) should therefore lower brain glycogen content. We tested this hypothesis by sleep depriving mice of three inbred strains, i.e., AKR/J (AK), DBA/2J (D2), and C57BL/6J (B6), that differ greatly in their sleep regulation. After a 6-h SD, these mice and their controls were killed by microwave irradiation, and glycogen and glucose were quantified in the cerebral cortex, brain stem, and cerebellum. After SD, both measures significantly increased by ϳ40% in the cortex of B6 mice, while glycogen significantly decreased by 20-38% in brain stem and cerebellum of AK and D2 mice. In contrast, after SD, glucose content increased in all three structures in AK mice and did not change in D2 mice. The increase in glycogen after SD in B6 mice persisted under conditions of food deprivation that, by itself, lowered cortical glycogen. Furthermore, the strains that differ most in their compensatory response to sleep loss, i.e., AK and D2, did not differ in their glycogen response. Thus glycogen content per se is an unlikely end point of sleep's functional role in brain energy homeostasis.mouse; sleep function and regulation; brain glycogen; glucose; energy homeostasis; food deprivation; halothane anesthesia COMPARED WITH WAKEFULNESS, non-rapid-eye-movement sleep (NREMS) is accompanied by a decrease in brain metabolism (reviewed in Ref. 26). These observations have led to several hypotheses concerning a functional link between sleep and energy homeostasis in the brain. We have advanced a hypothesis integrating both functional and regulatory aspects regarding sleep (3). As to sleep function, we proposed that cerebral glycogen stores, the most important energy store in the brain (19), are progressively depleted during wakefulness and have to be replenished during NREMS. As to sleep regulation, we implicated adenosine as a molecular feedback signal for sleep need (reviewed by Refs. 3,33,35). We proposed that glycogen depletion enhances extracellular adenosine release, thereby promoting sleep onset, sleep continuity, and NREMS delta power [i.e., EEG power in the 1-to 4-Hz range, a marker of NREMS need (5, 6, 12)].A sleep-regulatory role for adenosine has gained considerable support (reviewed by Ref. 33). A functional role for sleep in regulating glycogen content has received less attention. Recently, two studies directly tested this hypothesis by comparing brain glycogen between sleep-deprived and control rats. The results were inconclusive. In one study, a decrease in glycogen was observed throughout most of the brain of adult rats sleep deprived for 12 h or longer (21), thus supporting our hypothesis. In a developmental study from our own laboratory, glycogen was found to decrease after sleep deprivation (SD) in the cerebellum but not in the cortex of 24-to 50-day-old rats (15). Moreover, in 59-day-old rats (the oldest age group studied), glycogen increased i...

Glucocorticoids influence brain glycogen levels during sleep deprivation

“…The no. of animals in each group for glycogen and glucose are, respectively, Con (14,14), Con SD (9, 10), Adxϩ (15, 16), and Adxϩ SD (8,8). *Significant differences between sleep-deprived animals and control groups (P Ͻ 0.05).…”

“…While in one study, 12-h SD decreased glycogen in the cortex and in several other brain regions (hippocampus, striatum, midbrain, and thalamus) of adult rats (25), SD increased glycogen levels in the cortex of 59-day-old rats in another (16). Furthermore, 6-h SD had varied effects on brain glycogen levels in young rats (16) and adult inbred mouse strains (14). These studies found that 6-h SD increased glycogen in the cortex of C57BL/6J mice but not in 24-to 50-day-old rats or in AKR/J and DBA/2J mice.…”

“…Recent studies have explored the relationship between brain glycogen and sleep by measuring glycogen (14,16,25), as well as enzymatic activity and the expression of mRNA-encoding proteins involved in glycogen metabolism, in sleep-deprived animals (32). The hypothesis proposed by Benington and Heller (3) predicts that glycogen levels will decrease after sleep deprivation (SD).…”

Key Electrophysiological, Molecular, and Metabolic Signatures of Sleep and Wakefulness Revealed in Primary Cortical Cultures

“…How the changes in brain and body metabolism that occur with changes in behavioral states relate to sleep function remains, however, unknown. So far, the evidence is based on glucose metabolism or gene expression related to metabolism of lipids and proteins (Kennedy et al, 1982;Everson et al, 1994;Cirelli and Tononi, 2000b;Netchiporouk et al, 2001;Franken et al, 2003;Brown, 2004;Mackiewicz et al, 2007;Vyazovskiy et al, 2008a). Changes in metabolism in living animals are regulated both locally (activitydependent) and globally through circulating humoral factors.…”

The Primary Function of Rem Sleep

“…Increased cerebral glycogen metabolism has also been observed in organisms exerting effort (Gruetter, 2003). However, this is "an unlikely end point of sleep's functional role in brain energy homeostasis" (Franken,Gip,8 preliminary draft (9/24/2006) Hagiwara, Ruby, & Heller, 2003). Glucose still must be metabolized to generate ATP for the hippocampus.…”