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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

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 ear...

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Autores principales: Markova, Veronika, Holm, Charlotte, Pinborg, Anja Bisgaard, Thomsen, Lars Lykke, Moos, Torben
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789712/
https://www.ncbi.nlm.nih.gov/pubmed/31416268
http://dx.doi.org/10.3390/ph12030120
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author Markova, Veronika
Holm, Charlotte
Pinborg, Anja Bisgaard
Thomsen, Lars Lykke
Moos, Torben
author_facet Markova, Veronika
Holm, Charlotte
Pinborg, Anja Bisgaard
Thomsen, Lars Lykke
Moos, Torben
author_sort Markova, Veronika
collection PubMed
description 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.
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spelling pubmed-67897122019-10-16 Impairment of the Developing Human Brain in Iron Deficiency: Correlations to Findings in Experimental Animals and Prospects for Early Intervention Therapy Markova, Veronika Holm, Charlotte Pinborg, Anja Bisgaard Thomsen, Lars Lykke Moos, Torben Pharmaceuticals (Basel) Review 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. MDPI 2019-08-14 /pmc/articles/PMC6789712/ /pubmed/31416268 http://dx.doi.org/10.3390/ph12030120 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Markova, Veronika
Holm, Charlotte
Pinborg, Anja Bisgaard
Thomsen, Lars Lykke
Moos, Torben
Impairment of the Developing Human Brain in Iron Deficiency: Correlations to Findings in Experimental Animals and Prospects for Early Intervention Therapy
title Impairment of the Developing Human Brain in Iron Deficiency: Correlations to Findings in Experimental Animals and Prospects for Early Intervention Therapy
title_full Impairment of the Developing Human Brain in Iron Deficiency: Correlations to Findings in Experimental Animals and Prospects for Early Intervention Therapy
title_fullStr Impairment of the Developing Human Brain in Iron Deficiency: Correlations to Findings in Experimental Animals and Prospects for Early Intervention Therapy
title_full_unstemmed Impairment of the Developing Human Brain in Iron Deficiency: Correlations to Findings in Experimental Animals and Prospects for Early Intervention Therapy
title_short Impairment of the Developing Human Brain in Iron Deficiency: Correlations to Findings in Experimental Animals and Prospects for Early Intervention Therapy
title_sort impairment of the developing human brain in iron deficiency: correlations to findings in experimental animals and prospects for early intervention therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789712/
https://www.ncbi.nlm.nih.gov/pubmed/31416268
http://dx.doi.org/10.3390/ph12030120
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