Iron efflux from astrocytes plays a role in remyelination. J Neurosci 2012 Apr 04;32(14):4841-7
Date
04/12/2012Pubmed ID
22492039Pubmed Central ID
PMC6620916DOI
10.1523/JNEUROSCI.5328-11.2012Scopus ID
2-s2.0-84859361252 (requires institutional sign-in at Scopus site) 71 CitationsAbstract
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 SAuthor
Antje Kroner-Milsch MD, PhD Associate Professor in the Neurosurgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
Astrocytes
Cells, Cultured
Female
Iron
Male
Mice
Mice, Knockout
Myelin Sheath
Nerve Fibers, Myelinated
Oligodendroglia
