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Published on: November 29, 2019
Quantitative proteomic analyses of cerebrospinal fluid using iTRAQ in a primate model of iron deficiency anemia
Stephanie M Patton1, Christopher L Coe, Gabriele R Lubach
1Penn State University College of Medicine, Hershey, PA, USA. smp11@psu.edu
Insights
Early iron deficiency in infant monkeys causes lasting brain changes, affecting neuronal connections even after anemia is resolved. These alterations in neuroconnectivity may explain persistent cognitive and motor deficits.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Iron deficiency anemia impacts nearly 2 billion people globally, disproportionately affecting pregnant women and young children.
- Anemia during infancy can lead to persistent cognitive, attention, and motor deficits, even with iron treatment.
Purpose of the Study:
- To identify differential protein expression in cerebrospinal fluid (CSF) associated with early iron deficiency in infant primates.
- To investigate the long-term effects of early iron deficiency on brain development and neuroconnectivity.
Main Methods:
- iTRAQ (isobaric tag for relative and absolute quantitation) analysis was performed on CSF samples from iron-sufficient and iron-deficient anemic infant rhesus monkeys (Macaca mulatta).
- CSF was collected at weaning (6-7 months) and again at 12-14 months to assess changes over time.
Main Results:
- Despite iron repletion and normalization of hematological indices post-weaning, 5 CSF proteins remained differentially expressed in iron-deficient monkeys.
- The identified proteins are primarily involved in critical brain development processes, including neurite outgrowth, neuronal migration, and synapse formation.
- These findings suggest iron deficiency disrupts fundamental aspects of brain growth and neuronal connectivity.
Conclusions:
- Early-life iron deficiency induces significant, persistent alterations in neuroconnectivity in the developing brain.
- These changes in brain infrastructure may underlie observed behavioral and cognitive deficits that persist beyond the resolution of anemia.
- The study highlights the critical role of iron in establishing healthy brain architecture and function.
Abstract:
Iron deficiency affects nearly 2 billion people worldwide, with pregnant women and young children being most severely impacted. Sustained anemia during the first year of life can cause cognitive, attention and motor deficits, which may persist despite iron supplementation. We conducted iTRAQ analyses on cerebrospinal fluid (CSF) from infant monkeys (Macaca mulatta) to identify differential protein expression associated with early iron deficiency. CSF was collected from 5 iron-sufficient and 8 iron-deficient anemic monkeys at weaning age (6-7 months) and again at 12-14 months. Despite consumption of iron-fortified food after weaning, which restored hematological indices into the normal range, expression of 5 proteins in the CSF remained altered. Most of the proteins identified are involved in neurite outgrowth, migration or synapse formation. The results reveal novel ways in which iron deficiency undermines brain growth and results in aberrant neuronal migration and connections. Taken together with gene expression data from rodent models of iron deficiency, we conclude that significant alterations in neuroconnectivity occur in the iron-deficient brain, which may persist even after resolution of the hematological anemia. The compromised brain infrastructure could account for observations of behavioral deficits in children during and after the period of anemia.
