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.

Circadian rhythm of enolase in suprachiasmatic nucleus depends on mitochondrial function

“…The amplitude of the a-enolase mRNA rhythm was greater in the cortex than in the SCN. In our previous report, LDH activity was shown to have a circadian rhythm higher in the dark period than that in the light under the LD-entrained condition (Isobe et al, 2011). In addition, the LDHa and LDHb mRNAs were higher during the dark period under the LD cycle.…”

“…Metabolic activity in the SCN is higher during the light period, although the relationship with glucose concentration was not clearly explained until our previous report (Schwartz, 1991;Isobe et al, 2011). The glucose concentration is higher during the light period than in the dark.…”

“…In addition, the LDHa and LDHb mRNAs were higher during the dark period under the LD cycle. Both LDH enzyme activity and LDH coding mRNA peaked in the dark period (Isobe et al, 2011). The protein products of the clock-controlled gene mRNA, a-and g-enolase and LDHa and LDHb mRNA, are coupled to the metabolic state.…”

“…The relative mRNA level in the tissue blocks was quantified by quantitative RT-PCR as described previously (Isobe and Nishino, 2004;Isobe et al, 2011). Total RNA was isolated using Trizol (Invitrogen, Carlsbad, CA).…”

Brain Circadian Oscillators and Redox Regulation in Mammals

“…Morning glucose utilization in rat SCN is 2 · higher than in the evening ( p < 0.01). Mitochondrial cytochrome C oxidase activity, measured by the changes in light absorption at 550 nm, mitochondrial aggregation, and glucose concentration, is higher during the light period, as well (36). These measures of energetics find high-energy availability when SCN electrical activity also is high (82).…”