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Iron efflux from astrocytes plays a role in remyelination. J Neurosci 2012 Apr 04;32(14):4841-7

Date

04/12/2012

Pubmed ID

22492039

Pubmed Central ID

PMC6620916

DOI

10.1523/JNEUROSCI.5328-11.2012

Scopus ID

2-s2.0-84859361252   54 Citations

Abstract

How iron is delivered to the CNS for myelination is not well understood. We assessed whether astrocytes can provide iron to cells in the CNS for remyelination. To study this we generated a conditional deletion of the iron efflux transporter ferroportin (Fpn) in astrocytes, and induced focal demyelination in the mouse spinal cord dorsal column by microinjection of lysophosphatidylcholine (LPC). Remyelination assessed by electron microscopy was reduced in astrocyte-specific Fpn knock-out mice compared with wild-type controls, as was proliferation of oligodendrocyte precursor cells (OPCs). Cell culture work showed that lack of iron reduces the ability of microglia to express cytokines (TNF-α and IL-1β) involved in remyelination. Furthermore, astrocytes in culture express high levels of FGF-2 in response to IL-1β, and IGF-1 in response to TNF-α stimulation. FGF-2 and IGF-1 are known to be important for myelination. Reduction in IL-1β and IGF-1 were also seen in astrocyte-specific Fpn knock-out mice after LPC-induced demyelination. These data suggest that iron efflux from astrocytes plays a role in remyelination by either direct effects on OPCs or indirectly by affecting glial activation.

Author List

Schulz K, Kroner A, David S

Author

Antje Kroner-Milsch MD, PhD Assistant Professor in the Neurosurgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Astrocytes
Cells, Cultured
Female
Iron
Male
Mice
Mice, Knockout
Myelin Sheath
Nerve Fibers, Myelinated
Oligodendroglia