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Dopamine D₂ Receptor Expression Is Altered by Changes in Cellular Iron Levels in PC12 Cells and Rat Brain Tissue
- Unger, Erica L., Wiesinger, Jason A., Hao, Lei, Beard, John L.
- Journal of nutrition 2008 v.138 no.12 pp. 2487-2494
- dopamine, receptors, iron, dietary minerals, nutrient reserves, iron deficiency anemia, animal models, rats, cell lines, brain
- 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.