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Published on: July 12, 2012
Early-Life Iron Deficiency Anemia Programs the Hippocampal Epigenomic Landscape
Amanda K Barks1, Shirelle X Liu1, Michael K Georgieff1
1Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Insights
Iron deficiency anemia in early life can cause lasting neurodevelopmental deficits by altering gene expression. Iron-dependent epigenetic modifiers like JARID and TET proteins may explain how this occurs.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Iron deficiency (ID) anemia is a global health issue, particularly impacting pregnant women and young children.
- Early-life ID can lead to irreversible neurodevelopmental deficits, including cognitive impairment and neuropsychiatric disorders.
- Existing treatments for ID do not always reverse these long-term neurological consequences.
Purpose of the Study:
- To investigate the functional link between iron deficiency and gene dysregulation in the brain.
- To explore the role of iron-dependent epigenetic modifications in mediating the effects of early-life ID.
- To identify specific epigenetic modifiers involved in iron-mediated neurodevelopmental changes.
Main Methods:
- Utilized animal models of developmental iron deficiency.
- Examined hippocampal structure and function in affected models.
- Investigated gene expression patterns related to neurotransmission and synaptic plasticity.
- Focused on the role of iron-dependent epigenetic modifiers, specifically JARID and TET proteins.
Main Results:
- Developmental ID in animal models resulted in abnormal hippocampal structure and function.
- Observed dysregulation of genes critical for neurotransmission and synaptic plasticity.
- Identified iron-dependent epigenetic modifiers (JARID and TET proteins) as key players in neural development.
- These modifiers are implicated in establishing gene regulation during critical developmental periods.
Conclusions:
- Early-life iron deficiency can cause stable, life-long changes in gene regulation across the lifespan.
- Iron-dependent epigenetic mechanisms involving JARID and TET proteins are a likely cause of these persistent neurodevelopmental deficits.
- Understanding these mechanisms offers potential targets for mitigating the long-term effects of developmental iron deficiency.
Abstract:
Iron deficiency (ID) anemia is the foremost micronutrient deficiency worldwide, affecting around 40% of pregnant women and young children. ID during the prenatal and early postnatal periods has a pronounced effect on neurodevelopment, resulting in long-term effects such as cognitive impairment and increased risk for neuropsychiatric disorders. Treatment of ID has been complicated as it does not always resolve the long-lasting neurodevelopmental deficits. In animal models, developmental ID results in abnormal hippocampal structure and function associated with dysregulation of genes involved in neurotransmission and synaptic plasticity. Dysregulation of these genes is a likely proximate cause of the life-long deficits that follow developmental ID. However, a direct functional link between iron and gene dysregulation has yet to be elucidated. Iron-dependent epigenetic modifications are one mechanism by which ID could alter gene expression across the lifespan. The jumonji and AT-rich interaction domain-containing (JARID) protein and the Ten-Eleven Translocation (TET) proteins are two families of iron-dependent epigenetic modifiers that play critical roles during neural development by establishing proper gene regulation during critical periods of brain development. Therefore, JARIDs and TETs can contribute to the iron-mediated epigenetic mechanisms by which early-life ID directly causes stable changes in gene regulation across the life span.
