Diurnal variations in brain iron concentrations in BXD RI mice

Abstract

Under normal and dietary iron deficiency conditions, the BXD recombinant inbred (RI) strains of mice show large variations in regional brain iron concentration, particularly in the ventral midbrain (VMB). In a study utilizing just one of the BXD strains, diurnal changes in subregional brain iron concentration were found, which were dependent on the brain region and sex of the mice. The focus of this study was to determine if diurnal changes in VMB can be found across other BXD RI strains and whether a diurnal effect would be common to all strains or variable across strains similar to the large strain variability in iron concentrations determined during the first part of the light phase. Eight RI (BXD type) strains of mice of both sexes were selected for this study. Mice were sacrificed at postnatal day 120: half in the light phase (LP) and half in the dark phase (DP) of the light–dark cycle. Iron concentrations were determined in VMB, which was the primary region of interest, and five other brain regions. Exploratory analysis was also done on liver and spleen iron concentrations to assess for diurnal changes. Three strains showed clear diurnal variation in iron in the VMB and the others strains showed diurnal variations in other regions. These changes were not equally apparent in both sexes. Exploratory analysis also found strain×sex-dependent diurnal differences in spleen and liver iron. In conclusion, significant brain-regional-specific diurnal changes in total iron concentrations were found in a selection of BXD RI mice. Sex and strain are functional determinates of which regions will be affected and in what direction the affect will be. The study provides an animal model for future work into determining the biological and genetic basis of circadian influences on VMB iron homeostasis.