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Cord Blood-Derived Exosomal CNTN2 and BDNF: Potential Molecular Markers for Brain Health of Neonates at Risk for Iron Deficiency

Maternal iron deficiency anemia, obesity, and diabetes are prevalent during pregnancy. All are associated with neonatal brain iron deficiency (ID) and neurodevelopmental impairment. Exosomes are extracellular vesicles involved in cell–cell communication. Contactin-2 (CNTN2), a neural-specific glycop...

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Autores principales: Marell, Paulina S., Blohowiak, Sharon E., Evans, Michael D., Georgieff, Michael K., Kling, Pamela J., Tran, Phu V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835945/
https://www.ncbi.nlm.nih.gov/pubmed/31623079
http://dx.doi.org/10.3390/nu11102478
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author Marell, Paulina S.
Blohowiak, Sharon E.
Evans, Michael D.
Georgieff, Michael K.
Kling, Pamela J.
Tran, Phu V.
author_facet Marell, Paulina S.
Blohowiak, Sharon E.
Evans, Michael D.
Georgieff, Michael K.
Kling, Pamela J.
Tran, Phu V.
author_sort Marell, Paulina S.
collection PubMed
description Maternal iron deficiency anemia, obesity, and diabetes are prevalent during pregnancy. All are associated with neonatal brain iron deficiency (ID) and neurodevelopmental impairment. Exosomes are extracellular vesicles involved in cell–cell communication. Contactin-2 (CNTN2), a neural-specific glycoprotein, and brain-derived neurotrophic factor (BDNF) are important in neurodevelopment and found in exosomes. We hypothesized that exosomal CNTN2 and BDNF identify infants at risk for brain ID. Umbilical cord blood samples were measured for iron status. Maternal anemia, diabetes, and body mass index (BMI) were recorded. Cord blood exosomes were isolated and validated for the exosomal marker CD81 and the neural-specific exosomal marker CNTN2. Exosomal CNTN2 and BDNF levels were quantified by ELISA. Analysis of CNTN2 and BDNF levels as predictors of cord blood iron indices showed a direct correlation between CNTN2 and ferritin in all neonates (n = 79, β = 1.75, p = 0.02). In contrast, BDNF levels inversely correlated with ferritin (β = −1.20, p = 0.03), with stronger association in female neonates (n = 37, β = −1.35, p = 0.06), although there is no evidence of a sex-specific effect. Analysis of maternal risk factors for neonatal brain ID as predictors of exosomal CNTN2 and BDNF levels showed sex-specific relationships between infants of diabetic mothers (IDMs) and CNTN2 levels (Interaction p = 0.0005). While male IDMs exhibited a negative correlation (n = 42, β = −0.69, p = 0.02), female IDMs showed a positive correlation (n = 37, β = 0.92, p = 0.01) with CNTN2. A negative correlation between BNDF and maternal BMI was found with stronger association in female neonates (per 10 units BMI, β = −0.60, p = 0.04). These findings suggest CNTN2 and BNDF are respective molecular markers for male and female neonates at risk for brain ID. This study supports the potential of exosomal markers to assess neonatal brain status in at-risk infants.
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spelling pubmed-68359452019-11-25 Cord Blood-Derived Exosomal CNTN2 and BDNF: Potential Molecular Markers for Brain Health of Neonates at Risk for Iron Deficiency Marell, Paulina S. Blohowiak, Sharon E. Evans, Michael D. Georgieff, Michael K. Kling, Pamela J. Tran, Phu V. Nutrients Article Maternal iron deficiency anemia, obesity, and diabetes are prevalent during pregnancy. All are associated with neonatal brain iron deficiency (ID) and neurodevelopmental impairment. Exosomes are extracellular vesicles involved in cell–cell communication. Contactin-2 (CNTN2), a neural-specific glycoprotein, and brain-derived neurotrophic factor (BDNF) are important in neurodevelopment and found in exosomes. We hypothesized that exosomal CNTN2 and BDNF identify infants at risk for brain ID. Umbilical cord blood samples were measured for iron status. Maternal anemia, diabetes, and body mass index (BMI) were recorded. Cord blood exosomes were isolated and validated for the exosomal marker CD81 and the neural-specific exosomal marker CNTN2. Exosomal CNTN2 and BDNF levels were quantified by ELISA. Analysis of CNTN2 and BDNF levels as predictors of cord blood iron indices showed a direct correlation between CNTN2 and ferritin in all neonates (n = 79, β = 1.75, p = 0.02). In contrast, BDNF levels inversely correlated with ferritin (β = −1.20, p = 0.03), with stronger association in female neonates (n = 37, β = −1.35, p = 0.06), although there is no evidence of a sex-specific effect. Analysis of maternal risk factors for neonatal brain ID as predictors of exosomal CNTN2 and BDNF levels showed sex-specific relationships between infants of diabetic mothers (IDMs) and CNTN2 levels (Interaction p = 0.0005). While male IDMs exhibited a negative correlation (n = 42, β = −0.69, p = 0.02), female IDMs showed a positive correlation (n = 37, β = 0.92, p = 0.01) with CNTN2. A negative correlation between BNDF and maternal BMI was found with stronger association in female neonates (per 10 units BMI, β = −0.60, p = 0.04). These findings suggest CNTN2 and BNDF are respective molecular markers for male and female neonates at risk for brain ID. This study supports the potential of exosomal markers to assess neonatal brain status in at-risk infants. MDPI 2019-10-16 /pmc/articles/PMC6835945/ /pubmed/31623079 http://dx.doi.org/10.3390/nu11102478 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 Article
Marell, Paulina S.
Blohowiak, Sharon E.
Evans, Michael D.
Georgieff, Michael K.
Kling, Pamela J.
Tran, Phu V.
Cord Blood-Derived Exosomal CNTN2 and BDNF: Potential Molecular Markers for Brain Health of Neonates at Risk for Iron Deficiency
title Cord Blood-Derived Exosomal CNTN2 and BDNF: Potential Molecular Markers for Brain Health of Neonates at Risk for Iron Deficiency
title_full Cord Blood-Derived Exosomal CNTN2 and BDNF: Potential Molecular Markers for Brain Health of Neonates at Risk for Iron Deficiency
title_fullStr Cord Blood-Derived Exosomal CNTN2 and BDNF: Potential Molecular Markers for Brain Health of Neonates at Risk for Iron Deficiency
title_full_unstemmed Cord Blood-Derived Exosomal CNTN2 and BDNF: Potential Molecular Markers for Brain Health of Neonates at Risk for Iron Deficiency
title_short Cord Blood-Derived Exosomal CNTN2 and BDNF: Potential Molecular Markers for Brain Health of Neonates at Risk for Iron Deficiency
title_sort cord blood-derived exosomal cntn2 and bdnf: potential molecular markers for brain health of neonates at risk for iron deficiency
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835945/
https://www.ncbi.nlm.nih.gov/pubmed/31623079
http://dx.doi.org/10.3390/nu11102478
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