Alteration of brain glycogen turnover in the conscious rat after 5 h of prolonged wakefulness

Although glycogen (Glyc) is the main carbohydrate storage component, the role of Glyc in the brain during prolonged wakefulness is not clear. The aim of this study was to determine brain Glyc concentration ([]) and turnover time (τ) in euglycemic conscious and undisturbed rats, compared to rats maintained awake for 5 h. To measure the metabolism of [1-¹³C]-labeled Glc into Glyc, 23 rats received a [1-¹³C]-labeled Glc solution as drink (10% weight per volume in tap water) ad libitum as their sole source of exogenous carbon for a "labeling period" of either 5 h (n = 13), 24 h (n = 5) or 48 h (n = 5). Six of the rats labeled for 5 h were continuously maintained awake by acoustic, tactile and olfactory stimuli during the labeling period, which resulted in slightly elevated corticosterone levels. Brain [Glyc] measured biochemically after focused microwave fixation in the rats maintained awake (3.9 ± 0.2 μmol/g, n = 6) was not significantly different from that of the control group (4.0 ± 0.1 μmol/g, n = 7; t-test, P > 0.5). To account for potential variations in plasma Glc isotopic enrichment (IE), Glyc IE was normalized by N-acetyl-aspartate (NAA) IE. A simple mathematical model was developed to derive brain Glyc turnover time as 5.3 h with a fit error of 3.2 h and NAA turnover time as 15.6 h with a fit error of 6.5 h, in the control rats. A faster τ_Glyc (2.9 h with a fit error of 1.2 h) was estimated in the rats maintained awake for 5 h. In conclusion, 5 h of prolonged wakefulness mainly activates glycogen metabolism, but has minimal effect on brain [Glyc].