Acute and chronic effects of developmental iron deficiency on mRNA expression patterns in the brain

Department of Neurosurgery, M.S. Hershey Medical Center, Hershey, USA.
Journal of neural transmission. Supplementum (Impact Factor: 1.07). 02/2006; 71(71):173-96. DOI: 10.1007/978-3-211-33328-0_19
Source: PubMed


Because of the multiple biochemical pathways that require iron, iron deficiency can impact brain metabolism in many ways. The goal of this study was to identify a molecular footprint associated with ongoing versus long term consequences of iron deficiency using microarray analysis. Rats were born to iron-deficient mothers, and were analyzed at two different ages: 21 days, while weaning and iron-deficient; and six months, after a five month iron-sufficient recovery period. Overall, the data indicate that ongoing iron deficiency impacts multiple pathways, whereas the long term consequences of iron deficiency on gene expression are more limited. These data suggest that the gene array profiles obtained at postnatal day 21 reflect a brain under development in a metabolically compromised setting that given appropriate intervention is mostly correctable. There are, however, long term consequences to the developmental iron deficiency that could underlie the neurological deficits reported for iron deficiency.

9 Reads
  • Source
    • "Gene expression changes similar to those observed here may contribute to phenotypes involving movement impairment in various neurological disor- ders. There was very little overlap between the genes showing altered expression in response to iron supplementation and those identified in the microarray study by Clardy and colleagues (see Introduction), which investigated changes in rat brain gene expression in response to iron deficiency during development (Clardy et al., 2006). This suggests gene expression changes in adult iron overload are not simply the opposite of changes in developmental iron deficiency. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The effects of systemic iron overload on the brain are unclear. Microarray analysis of brain gene expression in mice following short-term iron supplementation revealed altered expression of 287 genes, although most changes were small. Transcripts for the iron storage protein ferritin light chain increased 20% (p=0.002) and transcripts for iron regulatory protein 1, which negatively regulates ferritin translation, decreased 28% (p=0.048). There were expression changes for genes involved in important brain functions such as neurotransmission and nitric oxide signaling, which is dependent on iron. Few changes related to reactive oxygen species, inflammation or apoptosis, however expression changes were observed for genes causatively linked to neurological disorders, including Charcot-Marie-Tooth disease, neuronal ceroid lipofuscinosis and mucolipidosis. The latter involve intralysosomal lipofuscin build-up that may reflect lysosomal iron accumulation. The findings suggest that high iron intake may cause subtle brain effects of clinical relevance in some circumstances.
    Neurochemistry International 03/2010; 56(6-7):856-63. DOI:10.1016/j.neuint.2010.03.015 · 3.09 Impact Factor
  • Source
    • "IDA humans also have a reduced capacity to thermoregulate that is related to loss of thyroid function (Borel et al. 1991). In a gene array study from our laboratory on young rats, the TH-binding protein mRNA showed the greatest response to ID during development (Clardy et al. 2006b). Thus, there appears to be a significant impact of ID on the thyroid system from the level of mRNA to post-translational modification of proteins. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Iron deficiency (ID) anemia during infancy results in long-term neurological consequences, yet the mediating mechanisms remain unclear. Infant monkeys often become naturally anemic during the first 6 months of life, presenting an opportunity to determine the effect of developmental iron deficiency. After weaning, animals were chosen randomly for supplementation with oral iron or, fed a standard commercial chow diet. The control group was never iron deficient. ID anemia was corrected by 12 months in both groups, as indicated by hematological parameters. CSF was collected for proteomic analysis at 12 months of age to assess the impact of developmental ID on the brain. The CSF proteome for both formerly iron deficient groups was similar and revealed 12 proteins with expression levels altered at least twofold. These proteins were identified by matrix assisted laser desorption ionization time-of-flight spectrometry and included prostaglandin D synthase, olfactory receptors and glial fibrillary acidic protein. Thus the proteomic analysis reveals a persistent effect of ID and provides insights into reports of disturbed sleep, hypomyelination and other behavioral alterations associated with ID. Furthermore, alterations in the CSF proteome despite normal hematologic parameters indicate that there is a hierarchical system that prioritizes repletion of red cell mass at the expense of the brain.
    Journal of Neurochemistry 05/2008; 105(1):127-36. DOI:10.1111/j.1471-4159.2007.05113.x · 4.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Infants are at high risk for iron deficiency and iron-deficiency anemia. This review summarizes evidence of long-term effects of iron deficiency in infancy. Follow-up studies from preschool age to adolescence report poorer cognitive, motor, and social-emotional function, as well as persisting neurophysiologic differences. Research in animal models points to mechanisms for such long-lasting effects. Potential mechanisms relate to effects of iron deficiency during brain development on neurometabolism, myelination, and neurotransmitter function.
    Nutrition Reviews 06/2006; 64(5 Pt 2):S34-43; discussion S72-91. DOI:10.1111/j.1753-4887.2006.tb00243.x · 6.08 Impact Factor
Show more

Similar Publications