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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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