THE CONSEQUENCES AND REVERSIBILITY OF CONGENITAL IRON DEFICIENCY ON THE AMOUNT OF NEURONS IN THE HIPPOCAMPAL AREA AND THE FATTY ACID COMPOSITION OF THE CEREBELLUM

Gall, Marco

4. term

Medicine with Industrial Specialisation, Master

2011

2011-05-15

38 pages

Abstract Background: Iron deficiency is the most prevalent nutritional disorder worldwide, especially among pregnant women and children. Congenital iron deficiency causes several deleterious effects on the cognitive and motoric development of the infant. Objective: The objective of this study is to assess the consequences of severe congenital iron deficiency on the neuron count in the hippocampus and the fatty acid composition of the cerebellum in male Wistar rats, and to discover whether or not iron supplementation injected during the window of opportunity, which is equivalent to the 3rd trimester in human development, can restore the deleterious effects of iron deficiency. Design: Adult female rats were randomly divided into two groups. The rats assigned for iron deficiency were exsangiunated and fed an iron depleted diet (<10mg Fe/kg), while the control rats were fed a commercial diet. The offspring of the iron deficient (ID) dams were designated into two groups, a treatment group where pups received iron injections (45mg/kg iron isomaltoside 1000) and a group receiving saline injections, thus remaining ID. The severity of iron deficiency was confirmed by measuring hematocrit values on postnatal day (P) 8-13, P15-18 and P86-94. A footprint analysis test was performed on male rats on P85-90 and the rats were euthanized on P86-94, and their brains were excised for brain iron analysis of the mesencephalon, stereological analysis of the hippocampus and fatty acid analysis. Results: The results of the footprint analysis showed significantly increased gait width in ID animals compared to both control and ID animals receiving iron supplement (ID + im1000). The fatty acid analysis showed a significant decrease in both docosahexaenoic acid (DHA) and total amount of polyunsaturated fatty acids (PUFAs) in the ID + im1000 group compared to the control group. Furthermore, the control group had a higher amount of n-3 fatty acids compared to both the ID and ID + im1000 group, and the ID group had a higher amount of n-6 fatty acids compared to the ID + im1000 and control group. The results of stereological counting of the hippocampus showed a larger amount of neurons in the dentate gyrus (DG) of the ID + im1000 groups compared to the ID group. Conclusion: The deleterious effects of congenital ID can be reversed to some degree by administering iron isomaltoside 1000 during the window of opportunity. While motor defects and low hematological values resulting from congenital ID are reversed completely, the results suggest that the lipid composition of the cerebellum cannot be fully recovered to that of normal individuals. In addition, the results suggest that the amount of neurons in the DG can be improved by administering iron in early life.

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