Circadian rhythm of metabolic oscillation in suprachiasmatic nucleus depends on the mitochondrial oxidation state, reflected by cytochrome C oxidase and lactate dehydrogenase

Abstract

Metabolic activity in the suprachiasmatic nucleus (SCN), a center of biological rhythm, is higher during the daytime than at night. The rhythmic oscillation in the SCN is feedback controlled by the Clock/Bmal1 heterodimer binding to the E-box in target genes (e.g., Arg-vasopressin). Similar transcriptional regulation by Npas2/Bmal1 heterodimer formation operates in the brain, which is dependent on the redox state (i.e., NAD/NADH). To clarify the metabolic function of SCN in relation to the redox state and glycolysis levels, we measured glucose, lactate dehydrogenase (LDH), LDH mRNA, and cytochrome C oxidase, energy-producing biochemical materials from mitochondria/cytosol, in rats kept under a light-dark cycle. Mitochondrial cytochrome C oxidase activity, measured by the changes in absorption at 550 nm, was higher during the light period than during the dark period. Glucose concentration was higher during the light period. In contrast, LDH and its coding mRNA were higher during the dark period. Mitochondrial aggregation, which is reflected by mitochondrial membrane potential, indexed by JC-1 fluorescence, was higher during the light period. The results indicate that the glycolysis energy pathway in the SCN, which exhits higher metabolic activity during the day than at night, might be involved in the generation of circadian rhythm.