INTRODUCTION REGULATION OF ENERGY SUPPLY FOR NEURONS INVOLVES A COMPLEX INTERACTION BETWEEN NEU- RONS AND ASTROCYTES.1-3 Astrocytes are the major source of glycogen in the brain and provide lactate to neurons by anaer-

REGULATION OF ENERGY SUPPLY FOR NEURONS INVOLVES A COMPLEX INTERACTION BETWEEN NEURONS AND ASTROCYTES.1-3 Astrocytes are the major source of glycogen in the brain and provide lactate to neurons by anaerobic glycolysis.4-6 Neurons contain the pathways for oxidative phosphorylation that are required for adenosine triphosphate (ATP) production to meet the demands of neuronal activity.7-9 Studies conducted on single-cell recordings have revealed that wake neurons are steadily depolarized and require more energy.10 In addition, a study on electroencephalogram (EEG)-implanted freely moving rats has shown that wake and sleep states are accompanied by redox changes in the brain in parallel to different energy demands.11 With prolonged wakefulness, there are alterations that occur in brain energy regulation. Changes in brain glycogen with increased wakefulness (activity) have been described in rodents in some,12 but not all13 studies and in Drosophila.14 In addition, local decreased rates of cerebral energy metabolism have been observed in hypothalamus, thalamus, and limbic system of freely moving rats while they were asleep.15 There is also indirect evidence that in the basal forebrain, there are likely alterations in oxidative phosphorylation leading to changes in ATP/adenosine diphosphate (ADP) levels, since it has been shown that adenosine, a byproduct of ATP hydrolysis and a potent neuromodulator, builds up during progressive increases in wakefulness,16-18 an observation compatible with the BeningtonHeller hypothesis of sleep homeostasis.19 Employing microarray and differential display techniques, recent studies in rat20-23 and in Drosophila24 have demonstrated an upregulation of the mRNA for 2 subunits of the mitochondrial respiratory chain, the subunit 2 (NDII) of complex I (NADH