Iron deficiency (ID) is one of the most prevalent nutritional deficiencies in the world. Iron deficiency in the late fetal and newborn period causes abnormal cognitive performance and emotional regulation, which can persist into adulthood despite iron repletion. Potential mechanisms contributing to these impairments include deficits in brain energy metabolism, neurotransmission, and myelination. Here, we comprehensively review the existing data that demonstrate diminished brain energetic capacity as a mechanistic driver of impaired neurobehavioral development due to early-life (fetal-neonatal) ID. We further discuss a novel hypothesis that permanent metabolic reprogramming, which occurs during the period of ID, leads to chronically impaired neuronal energetics and mitochondrial capacity in adulthood, thus limiting adult neuroplasticity and neurobehavioral function. We conclude that early-life ID impairs energy metabolism in a brain region- and age-dependent manner, with particularly strong evidence for hippocampal neurons. Additional studies, focusing on other brain regions and cell types, are needed.
Bibliographical noteFunding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The writing of this manuscript was supported by National Institutes of Health Grants R01 HD29241 (MKG), R01 HD094809 (MKG), R01 NS099178 (PVT), and R01 HD089989 (RR).
© The Author(s) 2020.
- brain development
- energy metabolism
- iron deficiency
PubMed: MeSH publication types
- Journal Article