Dopamine D2 Receptor Expression Is Altered by Changes in Cellular Iron Levels in PC12 Cells and Rat Brain Tissue

Abstract

Iron deficiency anemia in early life alters the development and functioning of the dopamine neurotransmitter system, but data regarding the specific effects of brain iron loss on dopamine D2 receptor regulation are lacking. Cell culture and animal models were employed in this study to determine whether D2 receptor expression is altered when cellular iron levels are depleted. Endogenous D2 receptor-expressing PC12 cells exposed to increasing concentrations of the iron chelator desferrioxamine (25–100 μmol/L) exhibited dose-dependent decreases in total D2 receptor protein concentrations (20–65%), but there were minimal effects on D2 receptor mRNA levels. When iron-deficient cells were repleted with ferric ammonium citrate for 24 h, D2 receptor protein densities were similar to control. Dietary iron deficiency for 6 wk in weanling rats also reduced regional iron concentrations by nearly 50% in the ventral midbrain and caudate but did not affect D2 receptor mRNA levels in the ventral midbrain. Iron deficiency significantly reduced membrane D2 receptor protein levels by >70% in caudate, whereas cytosolic concentrations showed only 25% losses. D2 receptor protein densities and regional iron concentrations were restored within 2 wk of dietary iron repletion. These results support the concept that D2 receptor gene expression is not significantly changed by iron deficiency, whereas dopamine receptor trafficking is affected and is likely related to known dopamine system alterations in iron deficiency.