Developmental changes in the expression of iron regulatory proteins and iron transport proteins in the perinatal rat brain

Asha Jyothi M. Siddappa, Raghavendra B. Rao, Jane D. Wobken, Elizabeth A. Leibold, James Connor, Michael K. Georgieff

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Abstract

The perinatal brain requires a tightly regulated iron transport system. Iron regulatory proteins (IRPs) 1 and 2 are cytosolic proteins that regulate the stability of mRNA for the two major cellular iron transporters, transferrin receptor (TfR) and divalent metal transporter-1 (DMT-1). We studied the localization of IRPs, their change in expression during perinatal development, and their relationship to TfR and DMT-1 in rat brain between postnatal days (PND) 5 and 15. Twelve-micron frozen coronal sections of fixed brain tissue were obtained from iron-sufficient Sprague-Dawley rat pups on PND 5, 10, and 15, and were visualized at 20 to 1,000X light microscopy for diaminobenzidine activity after incubation with specific primary IRP-1, IRP-2, DMT-1, and TfR antibodies and a universal biotinylated secondary and tertiary antibody system. IRP and transport protein expression increased in parallel over time. IRP1, IRP2, and DMT-1 were partially expressed in the choroid plexus epithelial cells at PND 5 and 10, and fully expressed at PND 15. The cerebral blood vessels and ependymal cells strongly expressed IRP1, IRP2, and DMT-1 as early as PND 5. Substantive TfR staining was not seen in the choroid plexus or ependyma until PND 15. Glial and neuronal expression of IRP1, IRP2, DMT-1, and TfR in cortex, hippocampal subareas and striatum increased over time, but showed variability in cell number and intensity of expression based on brain region, cell type, and age. These developmental changes in IRP and transporter expression suggest potentially different time periods of brain structure vulnerability to iron deficiency or iron overload.

Original languageEnglish (US)
Pages (from-to)761-775
Number of pages15
JournalJournal of Neuroscience Research
Volume68
Issue number6
DOIs
StatePublished - Jun 15 2002

Fingerprint

Iron-Regulatory Proteins
Protein Transport
Transferrin Receptors
Carrier Proteins
Iron
Iron Regulatory Protein 2
Iron Regulatory Protein 1
Brain
Choroid Plexus
Ependyma
Iron Overload
Antibodies
Protein Stability
Frozen Sections
Neuroglia
Blood Vessels
Sprague Dawley Rats
solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
Microscopy
Cell Count

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

Siddappa, Asha Jyothi M. ; Rao, Raghavendra B. ; Wobken, Jane D. ; Leibold, Elizabeth A. ; Connor, James ; Georgieff, Michael K. / Developmental changes in the expression of iron regulatory proteins and iron transport proteins in the perinatal rat brain. In: Journal of Neuroscience Research. 2002 ; Vol. 68, No. 6. pp. 761-775.
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Developmental changes in the expression of iron regulatory proteins and iron transport proteins in the perinatal rat brain. / Siddappa, Asha Jyothi M.; Rao, Raghavendra B.; Wobken, Jane D.; Leibold, Elizabeth A.; Connor, James; Georgieff, Michael K.

In: Journal of Neuroscience Research, Vol. 68, No. 6, 15.06.2002, p. 761-775.

Research output: Contribution to journalArticle

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AU - Rao, Raghavendra B.

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AU - Connor, James

AU - Georgieff, Michael K.

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