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Changes in Brain Gene Expression in Nutrient Deficiencies: An Example with Iron

  • Erica L. Unger
  • Narasimha Hegde
  • James R. Connor
Chapter

Abstract

Iron is an important element in biological systems, and cellular iron uptake, distribution, and export must be tightly regulated, as both iron deficiency and overload can have deleterious effects on protein, nucleic acid, and lipid contents of the cell. The brain is the organ most vulnerable to iron deficiency during critical periods of development, particularly during the last trimester of fetal life and during the period of brain growth spurt and differentiation. Rodent models have shown that iron deficiency in early life and during adolescence affects both gene expression and the protein levels of a variety of proteins. Genes that are altered by brain iron deficiency are integral to processes including signal transduction, myelin formation, cell growth, energy metabolism, and neurotransmitter signaling. Further, oxidative stress gene profiles of the iron-deficient brain appear similar to those observed in Alzheimer’s disease where iron overaccumulates in neuritic plaques. From the existing literature, it is apparent that while the expression level of many genes can be corrected with iron supplementation, other genes may not be responsive to iron treatment. The presence of genes that are not responsive to treatment suggests that many aspects of brain functioning are likely altered throughout the lifetime leading to undesirable behavioral outcomes.

Keywords

Iron Deficiency Transferrin Receptor Iron Homeostasis Divalent Metal Transporter Locus Ceruleus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

CSF

Cerebrospinal fluid

IF

Interstitial fluid

Tim-2

T-cell immunoglobulin and mucin domain-containing protein 2

IRP

Iron regulatory protein

IRE

Iron responsive element

UTR

Untranslated region

mTOR

Mammalian target of rapamycin

CamK2a

Calcium/calmodulin-dependent protein kinase II alpha

BDNF

Brain derived neurotrophic factor

ARA

Arachidonic acid

MBP

Myelin basic protein

MOG

Myelin-oligodendrocyte glycoprotein

MAL

Myelin and lymphocyte protein

MOBP

Myelin-associated oligodendrocytic basic protein

PMP22

Peripheral myelin protein 22

PLP

Proteolipid protein

DAT

Dopamine transporter

GABA

Gamma-aminobutyric acid

GAT1

Gamma-aminobutyric acid transporter type 1

VMAT2

Vesicular monoamine transporter 2

trkB

Tyrosine kinase B

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Erica L. Unger
    • 1
  • Narasimha Hegde
  • James R. Connor
  1. 1.Department of Nutritional SciencesPennsylvania State UniversityUniversity ParkUSA

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