Impairment of the Developing Human Brain in Iron Deficiency

Correlations to Findings in Experimental Animals and Prospects for Early Intervention Therapy

Veronika Markova, Charlotte Holm, Anja Bisgaard Pinborg, Lars Lykke Thomsen, Torben Moos

Publikation: Bidrag til tidsskriftReview (oversigtsartikel)Forskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftPharmaceuticals
Vol/bind12
Udgave nummer3
ISSN1424-8247
DOI
StatusUdgivet - 14 aug. 2019

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Secondary Prevention
Iron
Brain
Transferrin Receptors
Sus scrofa
Motor Skills
Myelin Sheath
Primates
Blood Vessels
Cerebrospinal Fluid
Rodentia
Blood Cells
Stem Cells
Biomarkers

Citer dette

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abstract = "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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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.

I: Pharmaceuticals, Bind 12, Nr. 3, 14.08.2019.

Publikation: Bidrag til tidsskriftReview (oversigtsartikel)Forskningpeer review

TY - JOUR

T1 - Impairment of the Developing Human Brain in Iron Deficiency

T2 - Correlations to Findings in Experimental Animals and Prospects for Early Intervention Therapy

AU - Markova, Veronika

AU - Holm, Charlotte

AU - Pinborg, Anja Bisgaard

AU - Thomsen, Lars Lykke

AU - Moos, Torben

PY - 2019/8/14

Y1 - 2019/8/14

N2 - 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.

AB - 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.

U2 - 10.3390/ph12030120

DO - 10.3390/ph12030120

M3 - Review article

VL - 12

JO - Pharmaceuticals

JF - Pharmaceuticals

SN - 1424-8247

IS - 3

ER -