Diurnal cycle influences peripheral and brain iron levels in mice

Abstract

Iron movement between organ pools involves a dynamic equilibrium of iron efflux and uptake, and homeostatic mechanisms are likely involved in providing iron to cells and organs when required. Daily iron levels in the plasma pool fluctuate with the diurnal cycle, but clear explanations regarding the objectives and regulation of the flux are lacking. The association between diurnal cycle and iron flux is relevant in the disease of restless legs syndrome (RLS), where individuals display diurnal deficits in motor control, have impaired brain iron metabolism, and perhaps altered iron uptake from the plasma pool. The goal of the present study was to examine diurnal variations in peripheral and regional brain iron to evaluate iron flux between organs in iron-sufficient and iron-deficient mice. In mice fed control diet, liver iron was elevated 30–40%, and plasma iron was reduced 20–30% in the active dark period compared with the inactive light phase. Dietary iron deficiency eliminated this variation in liver iron in male and female mice and in plasma iron in male mice. Reductions in ventral midbrain and nucleus accumbens iron and ferritin were apparent in iron-deficient mice during both diurnal phases, but only during the light phase was an ∼25% reduction in whole brain iron observed, suggesting different brain iron requirements between phases. These data demonstrate that iron flux between organs is sensitive to diurnal regulatory biology. Importantly, variations in brain iron may have temporal implications regarding neural functioning and may contribute to the diurnal cycle-dependent symptoms of RLS.