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Impairment of the Developing Human Brain in Iron Deficiency: Correlations to Findings in Experimental Animals and Prospects for Early Intervention Therapy

1
Department of Obstetrics and Gynaecology, Hvidovre Hospital, Copenhagen University Hospital, 2650 Hvidovre, Denmark
2
Pharmacosmos A/S, 4300 Holbæk, Denmark
3
Laboratory of Neurobiology, Department of Health Science and Technology, Aalborg University, 9220 Aalborg, Denmark
4
Fertility Clinic, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2019, 12(3), 120; https://doi.org/10.3390/ph12030120
Received: 17 July 2019 / Revised: 12 August 2019 / Accepted: 13 August 2019 / Published: 14 August 2019
(This article belongs to the Special Issue Iron as Therapeutic Targets in Human Diseases)
Due to the necessity of iron for a variety of cellular functions, the developing mammalian organism is vulnerable to iron deficiency, hence causing structural abnormalities and physiological malfunctioning in organs, which are particularly dependent on adequate iron stores, such as the brain. In early embryonic life, iron is already needed for proper development of the brain with the proliferation, migration, and differentiation of neuro-progenitor cells. This is underpinned by the widespread expression of transferrin receptors in the developing brain, which, in later life, is restricted to cells of the blood–brain and blood–cerebrospinal fluid barriers and neuronal cells, hence ensuring a sustained iron supply to the brain, even in the fully developed brain. In embryonic human life, iron deficiency is thought to result in a lower brain weight, with the impaired formation of myelin. Studies of fully developed infants that have experienced iron deficiency during development reveal the chronic and irreversible impairment of cognitive, memory, and motor skills, indicating widespread effects on the human brain. This review highlights the major findings of recent decades on the effects of gestational and lactational iron deficiency on the developing human brain. The findings are correlated to findings of experimental animals ranging from rodents to domestic pigs and non-human primates. The results point towards significant effects of iron deficiency on the developing brain. Evidence would be stronger with more studies addressing the human brain in real-time and the development of blood biomarkers of cerebral disturbance in iron deficiency. Cerebral iron deficiency is expected to be curable with iron substitution therapy, as the brain, privileged by the cerebral vascular transferrin receptor expression, is expected to facilitate iron extraction from the circulation and enable transport further into the brain. View Full-Text
Keywords: developmental; iron deficiency anemia; neonatal; transferrin receptor; treatment developmental; iron deficiency anemia; neonatal; transferrin receptor; treatment
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Markova, V.; Holm, C.; Pinborg, A.B.; Thomsen, L.L.; Moos, T. Impairment of the Developing Human Brain in Iron Deficiency: Correlations to Findings in Experimental Animals and Prospects for Early Intervention Therapy. Pharmaceuticals 2019, 12, 120.

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