Cord blood-derived exosomal CNTN2 and BDNF: Potential molecular markers for brain health of neonates at risk for iron deficiency

Paulina S. Marell, Sharon E. Blohowiak, Michael D. Evans, Michael K. Georgieff, Pamela J. Kling, Phu V. Tran

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number2478
JournalNutrients
Volume11
Issue number10
DOIs
StatePublished - Oct 2019

Bibliographical note

Funding Information:
Funding: We thank our sources of financial support: The Gerber Foundation, the Masonic Children’s Hospital Research Fund for Neurodevelopment & Child Mental Health Development, the University of Minnesota Department of Pediatric “R” Award. This research was supported by the National Institutes of Health’s National Center for Advancing Translational Sciences, grant UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health’s National Center for Advancing Translational Sciences.

Funding Information:
The Gerber Foundation, the Masonic Children?s Hospital Research Fund for Neurodevelopment & Child Mental Health Development, the University of Minnesota Department of Pediatric ?R? Award. This research was supported by the National Institutes of Health?s National Center for Advancing Translational Sciences, grant UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health?s National Center for Advancing Translational Sciences.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Brain
  • Diabetes
  • Neurodevelopment
  • Nutrition
  • Obesity

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