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Heterogenous distribution of ferroportin-containing neurons in mouse brain

BioMetals volume 24, pages 357–375 (2011)Cite this article

Abstract

Iron is crucial for a variety of cellular functions in neuronal cells. Neuronal iron uptake is reflected in a robust and consistent expression of transferrin receptors and divalent metal transporter 1 (DMT 1). Conversely, the mechanisms by which neurons neutralize and possibly excrete iron are less clear. Studies indicate that neurons express ferroportin which could reflect a mechanism for iron export. We mapped the distribution of ferroportin in the adult mouse brain using an antibody prepared from a peptide representing amino acid sequences 223–303 of mouse ferroportin. The antibody specifically detected ferroportin in brain homogenates, whereas homogenates of cultured endothelial cells were devoid of immunoreactivity. In brain sections, ferroportin was confined to neuronal cell bodies and peripheral processes of cerebral cortex, hippocampus, thalamus, brain stem, and cerebellum. In brain stem ferroportin-labeling was particularly high in neurons of cranial nerve nuclei and reticular formation. Ferroportin was hardly detectable in striatum, pallidum, or hypothalamus. Among non-neuronal cells, ferroportin was detected in oligodendrocytes and choroid plexus epithelial cells. A comparison with previous studies on the distribution of transferrin receptors in neurons shows that many neuronal pools coincide with those expressing ferroportin. The data therefore indicate that neuronal iron homeostasis consists of a delicate balance between transferrin receptor-mediated uptake of iron-transferrin and ferroportin-related iron excretion. The findings also suggest a particular high turnover of iron in neuronal regions, such as habenula, hippocampus, reticular formation and cerebellum, as several neurons in these regions exhibit a prominent co-expression of transferrin receptors and ferroportin.

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Abbreviations

3N:

Oculomotor nucleus

3V:

3rd ventricle

5N:

Motor trigeminal nucleus

7N:

Facial nucleus

M1:

Primary motor cortex

Amb:

Ambiguus nucleus

bEnd3:

Mouse brain endothelial cells

CA1:

Field CA1 of Ammon’s horn

CA2:

Field CA2 of Ammon’s horn

CA3:

Field CA3 of Ammon’s horn

cc:

Corpus callosum

CP:

Choroid plexus

D3V:

Dorsal part of the third ventricle

DAB:

3,3-Diaminobenzidine tetrahydrochloride

DG:

Dentate gyrus

DMT 1:

Divalent metal transporter 1

DR:

Dorsal raphe nucleus

EPl:

External plexiform layer of the olfactory bulb

EPlA:

External plexiform layer of the accessory olfactory bulb

Fpn-ir:

Ferroportin-immunoreactivity

Gl:

Glomerular layer of the olfactory bulb

GrO:

Granular cell layer of the olfactory bulb

hbc:

Habenular commissure

hi:

Habenulo-interpeduncular tract

IntP:

Interposed cerebellar nucleus posterior part

IG:

Induseum griseum

IP:

Interpeduncular nucleus

IPl:

Internal plexiform layer of the olfactory bulb

Lat:

Lateral cerebellar nucleus

LC:

Locus coeruleus

LHb:

Lateral habenular nucleus

ME:

Median eminence

Med:

Medial cerebellar nucleus

MHb:

Medial habenular nucleus

Mi:

Mitral cell layer of the olfactory bulb

Pir:

Piriform cortex

PPBS:

Potassium phosphate-buffered saline

Rbd:

Rhabdoid nucleus

RT:

Reverse transcriptase

TSA:

Tyramid signal amplification

UTR:

Untranslated region

VM:

Ventral medial thalamic nucleus

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Acknowledgments

We would like to thank Susan Peters at University of Copenhagen, Denmark and Merete Fredsgaard, Aalborg University, Denmark for excellent technical assistance. Murine brain endothelioma cells, bEnd3, were kindly obtained from Dr. Sara Gosk, University of Bonn, Germany. This work was supported by grants from the Lundbeck Fund, the Danish Parkinson’s Disease Fund, the Carlsberg Foundation, the Spar Nord Fund, and the Obelske Familiefond.

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Affiliations

  1. Section of Neurobiology, Biomedicine, Department of Health Science and Technology, Aalborg University, Fr. Bajers Vej 3B, 1.216, 9220, Aalborg East, Denmark

    Michael W. Boserup, Jacek Lichota & Torben Moos

  2. South Texas Veterans Health Care System, San Antonio, TX, USA

    David Haile

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  1. Michael W. Boserup
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  2. Jacek Lichota
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  3. David Haile
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  4. Torben Moos
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Correspondence to Torben Moos.

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Boserup, M.W., Lichota, J., Haile, D. et al. Heterogenous distribution of ferroportin-containing neurons in mouse brain. Biometals 24, 357–375 (2011). https://doi.org/10.1007/s10534-010-9405-2

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  • DOI: https://doi.org/10.1007/s10534-010-9405-2

Keywords

  • Blood–brain barrier
  • Iron
  • Neurodegeneration
  • Oxidative stress
  • qPCR
  • Transferrin