Sex and Genetics are Important Cofactors in Assessing the Impact of Iron Deficiency on the Developing Mouse Brain

The present study was designed to investigate the possible role of genetic background and sex in the behavioral and neurochemical responses to early iron deficiency. Male and female C57 and DBA mice were provided either an iron deficient (ID) or control (CN) diet during early growth periods. Dopamine D2 receptor densities, and dopamine and serotonin transporter densities were determined in specific brain regions. Iron deficient DBA mice had significantly lower D2 receptor densities in the frontal cortex (FC) and caudate putamen (CP) (19 vs. 35fmol/mg and 145 vs. 215 fmol/mg, respectively). Serotonin (5-HT) transporter densities in FC of iron deficient C57 mice tended to be lower than in control animals (40 vs. 60 fmol/mg) while in the nucleus accumbens (NA) the 5-HT transporter increased in density relative to controls (350 vs. 210 fmol/mg). Open field behaviors in naïve and cocaine treated mice were also affected by diet, suggesting that iron deficiency causes decreased dopamine output. These data indicate a substantial genetic-based variability in brain responses to iron deficiency anemia, some of which are in direct contrast to what other experimental data would have predicted. Future studies clearly need to consider genetic background and sex in their analytical approach.