Dietary iron deficiency in strain 40 BXD mice causes diurnal‐dependent alterations in brain iron and activity

Abstract

There is an existent literature on Restless Legs Syndrome that supports a role for regional brain iron, dopamine and diurnal cycle variations in its pathophysiology. In this study, Strain 40 of the BXD/Ty RI panel was utilized based on its mid‐range ventral midbrain iron levels among 30 BXD/Ty RI strains initially analyzed. Mice were challenged with control or iron restricted diets from postnatal day 21 to 120 and then brain iron, striatal extracellular dopamine, home‐cage locomotor activity and body temperature were assessed across the diurnal cycle. At day 120, mice fed an iron deficient (ID) diet showed reduced hemoglobin, hematocrit and spleen and liver iron compared to controls. Male and female ID mice displayed diurnal dependent decreases in ventral midbrain iron, while in nucleus accumbens, iron content was reduced only in male ID mice. Diurnal monitoring of home cage activity and body temperature revealed that iron deficiency alters the number and duration of activity cycles in the four hours surrounding the light transitions. During these transition periods, activity increased and decreased at a similar rate as extracellular dopamine and body temperature in control mice and ID females, while these transitions were blunted in ID males. These results suggest that dietary iron deficiency in BXD Strain 40 mice produces diurnal‐dependent alterations in brain iron in dopaminergic regions and in activity patterns.