Impact of Brain Iron Levels on Dopamine Metabolism
Open Access
- Author:
- Russo, Sabrina Ann
- Area of Honors:
- Nutritional Sciences
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Erica Unger, Thesis Supervisor
Dr. Erica Unger, Thesis Supervisor
Rebecca L Corwin, Thesis Honors Advisor - Keywords:
- Iron
Fe
Dopamine
DA
Restless Leg Syndrome
RLS
Fe deficiency - Abstract:
- ABSTRACT Iron (Fe) deficiency is one of the most common nutrient deficiencies in the world. Deficiency may occur due to decreased absorption rates that do not meet an individual’s needs or by an excessive rate of excretion via blood loss. Iron deficiency causes a reduction in iron levels in the brain, which causally leads to numerous negative behavioral outcomes. Fe functions in a number of bodily processes, including oxygen transport, facilitating electron transport in cytochromes, acting as monooxygenases, dioxygenases and peroxidases, and assisting the synthesis of niacin, hydroxylysine, myelin and neurotransmitters. One major neurotransmitter that is dependent upon Fe is dopamine (DA). DA is synthesized via a two-step process, and Fe is the cofactor of the initial step in DA production. Fe deficiency, therefore, may cause a secondary deficiency in DA. Fe and DA deficiencies are related to several disease states, including Restless Legs Syndrome. To investigate the effects of iron status on dopamine metabolism in the brain, iron levels in the dopamine cell body region, the ventral midbrain, were manipulated and the effects on the dopamine transporter (DAT) in terminal regions (striatum and prefrontal cortex) were investigated. Several experiments were conducted on three groups of rats (Fe sulfate-, saline- and DFO-infusion) to examine how differing levels of brain Fe may affect DA metabolism. Infusion of the iron chelator, desferrioxamine (DFO), resulted in a reduction in prefrontal cortex (PFC) and striatal DAT on the cellular membrane without changing cytosolic DAT levels. Cytosolic levels of PFC DAT were increased in iron-infused rats compared to saline-treated animals. Overall, these data support a role for VMB iron levels in regulating DAT trafficking in dopamine terminal regions.