(23) Effects of Choline as an Adjunct Therapy in an Iron Deficiency Model

Sophia K. Ostergren, University of Minnesota, Minneapolis, MN, United States; Michael Georgieff, University of Minnesota Medical School, United States; Thomas Bastian, University of Minnesota Medical School, United States

Background: Iron deficiency (ID) is one of the most prevalent nutritional deficiencies worldwide. ID is common in pregnant women and children, affecting on average 40-50% of these populations. ID in fetuses and newborns can result in long lasting neurobehavioral issues (e.g., deficits in hippocampal-mediated learning/memory). ID impairs mitochondrial respiration, ATP production, and dendritic complexity in the developing brain, with the greatest effect on hippocampal neurons. Iron repletion is insufficient to reverse the metabolic, neuron structural, or damage. Thus, an alternate or adjunct therapy is needed. Choline supplementation within the critical period of iron-dependent neuron development improves dendrite structural complexity, without altering mitochondrial respiration, following ID.

Objectives: The objective of this study was to test the hypothesis that adjunct choline treatment, when combined with iron repletion, can fully rescue neuronal energy status and structural complexity following ID in developing neuron cultures.

Design/Methods: Hippocampal neuronal cultures were made iron-deficient by adding the iron chelator deferoxamine (DFO) beginning at 3 days in vitro (DIV). At 14 DIV, during the energy-dependent period of neuronal structural development, iron-deficient cultures were treated with varying doses of choline, with and without concomitant iron repletion, or left untreated. Neuronal ATP levels and dendrite and synapse complexity were quantified after 7 days of treatment (i.e., 21 DIV).

Results: DFO significantly reduced 21 DIV neuronal ATP levels by 50% (p < 0.05). When given from 14 to 21 DIV, iron and 10, 30, and 90µM choline treatments all partially restore ATP levels (72-85% of iron-sufficient control). Neuronal ATP levels were fully rescued when choline and iron treatments were combined. Iron treatment did not fully rescue the ID-induced deficits in dendrite complexity and synapse density during this period. We are currently quantifying the effect of combined iron and choline treatments on these neuron structural outcomes.

Conclusion: Our findings show choline improves neuronal ATP production, an iron-dependent function critical for neuronal development, in developing iron-deficient neurons. Choline’s full rescue of neuronal ATP production when combined with iron repletion suggests choline may have therapeutic potential for iron-deficient children when iron supplementation alone is insufficient.