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Published on: August 25, 2014
DNA Methylation, Inflammation, and Neurobehavior in Preterm Infants
Marliese Dion Nist1, Rita H Pickler1, Abigail B Shoben2
1College of Nursing, The Ohio State University, Columbus, OH, USA.
Insights
Inflammation impacts preterm infant neurodevelopment via DNA methylation of brain-derived neurotrophic factor (BDNF) and nuclear factor-kappa-B-inhibitor alpha (NFKBIA) genes. Sex differences suggest females may be more vulnerable to inflammatory effects on neurobehavior.
Area of Science:
- Neuroscience
- Developmental Biology
- Epigenetics
Background:
- Inflammation is linked to neurodevelopmental disparities in preterm infants.
- DNA methylation may mediate inflammation's effects on gene expression, influencing neurodevelopment.
- Brain-derived neurotrophic factor (BDNF) and nuclear factor-kappa-B-inhibitor alpha (NFKBIA) are key genes in neurodevelopment and inflammation pathways.
Purpose of the Study:
- To investigate associations between inflammatory factors and DNA methylation of BDNF and NFKBIA.
- To examine the relationship between BDNF and NFKBIA methylation and early neurobehavior in preterm infants.
- To explore potential sex differences in these associations.
Main Methods:
- Longitudinal cohort study of preterm infants (28-31 weeks gestational age).
- Weekly blood sampling for inflammatory factor quantification.
- DNA methylation analysis of specific BDNF and NFKBIA CpG sites from saliva samples.
- Neurobehavioral assessment using the Neurobehavioral Assessment of the Preterm Infant.
Main Results:
- In females, inflammatory factors correlated positively with BDNF methylation and negatively with NFKBIA methylation at certain sites.
- In males, interleukin-6 showed negative associations with both BDNF and NFKBIA methylation.
- Female infants showed inverse associations between BDNF methylation and motor performance; male infants showed an inverse association between NFKBIA methylation and motor performance.
Conclusions:
- Evidence supports a mechanistic link between inflammation, DNA methylation, and neurobehavior in preterm infants.
- Sex-specific differences in methylation patterns and neurobehavioral outcomes were observed.
- Female infants may exhibit increased vulnerability to inflammation's neurodevelopmental impact, meriting further investigation.
Abstract:
Objectives: Inflammation contributes to disparate neurodevelopmental outcomes between preterm and term-born infants. In this context, DNA methylation may contribute to inflammation by affecting gene expression. Brain-derived neurotrophic factor (BDNF) and nuclear factor-kappa-B-inhibitor alpha (NFKBIA) are important genes for targeted DNA methylation analysis. The aims of this study were to (1) identify associations between inflammatory factors and BDNF and NFKBIA methylation, and (2) identify associations between BDNF and NFKBIA methylation and early neurobehavior in preterm infants. Methods: In a longitudinal cohort study of preterm infants born 28-31 weeks gestational age, blood samples were collected weekly for the quantification of inflammatory factors. We extracted DNA from saliva samples and quantified methylation of six BDNF cytosine-phosphate-guanine (CpG) sites and five NFKBIA CpG sites. Neurobehavior was assessed using the Neurobehavioral Assessment of the Preterm Infant. Results: Sixty-five infants were included in the analysis. In females, inflammatory factors were positively associated with BDNF methylation of most CpG sites. Interleukin-1 receptor antagonist was negatively associated with NFKBIA methylation at two CpG sites. In males, interleukin-6 was negatively associated with BDNF and NFKBIA methylation at most CpG sites. In females, BDNF methylation at two sites was inversely associated with motor performance. In males, NFKBIA methylation at one site was inversely associated with motor performance. Conclusion: This study provides evidence for the relationship between inflammation and neurobehavior in preterm infants, working mechanistically through DNA methylation. The finding of a difference between males and females suggests that female infants are potentially more vulnerable to inflammation and warrants future study.
