Potential role of iron in repair of inflammatory demyelinating lesions.
Adult
Aged
Animals
Callithrix
Demyelinating Diseases
/ metabolism
Encephalomyelitis, Autoimmune, Experimental
/ metabolism
Female
Humans
Inflammation
/ metabolism
Iron
/ metabolism
Macrophages
/ metabolism
Male
Microglia
/ metabolism
Middle Aged
Models, Neurological
Multiple Sclerosis
/ metabolism
Receptors, Transferrin
/ metabolism
Remyelination
Multiple sclerosis
Neuroscience
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
01 10 2019
01 10 2019
Historique:
received:
14
12
2018
accepted:
16
07
2019
pubmed:
10
9
2019
medline:
9
6
2020
entrez:
10
9
2019
Statut:
ppublish
Résumé
Inflammatory destruction of iron-rich myelin is characteristic of multiple sclerosis (MS). Although iron is needed for oligodendrocytes to produce myelin during development, its deposition has also been linked to neurodegeneration and inflammation, including in MS. We report perivascular iron deposition in multiple sclerosis lesions that was mirrored in 72 lesions from 13 marmosets with experimental autoimmune encephalomyelitis. Iron accumulated mainly inside microglia/macrophages from 6 weeks after demyelination. Consistently, expression of transferrin receptor, the brain's main iron-influx protein, increased as lesions aged. Iron was uncorrelated with inflammation and postdated initial demyelination, suggesting that iron is not directly pathogenic. Iron homeostasis was at least partially restored in remyelinated, but not persistently demyelinated, lesions. Taken together, our results suggest that iron accumulation in the weeks after inflammatory demyelination may contribute to lesion repair rather than inflammatory demyelination per se.
Identifiants
pubmed: 31498148
pii: 126809
doi: 10.1172/JCI126809
pmc: PMC6763243
doi:
pii:
Substances chimiques
Receptors, Transferrin
0
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4365-4376Références
Ann Neurol. 2014 Oct;76(4):594-608
pubmed: 25088017
Dev Biol. 2001 Sep 1;237(1):232-43
pubmed: 11518519
PLoS One. 2013;8(3):e57573
pubmed: 23516409
Brain. 2018 Jun 1;141(6):1637-1649
pubmed: 29688408
J Magn Reson Imaging. 2009 Mar;29(3):537-44
pubmed: 19243035
Gastroenterology. 2011 Jun;140(7):2044-55
pubmed: 21419768
Neuroimage. 2012 Jan 16;59(2):979-85
pubmed: 21906687
J Clin Invest. 2007 Jul;117(7):1926-32
pubmed: 17557118
AJNR Am J Neuroradiol. 2016 Sep;37(9):1629-35
pubmed: 27256856
Nat Rev Neurol. 2014 Aug;10(8):459-68
pubmed: 25002107
J Clin Invest. 2016 Jul 1;126(7):2597-609
pubmed: 27270171
Mult Scler. 1996 Oct;2(3):157-60
pubmed: 9345380
PLoS Pathog. 2013 Jan;9(1):e1003138
pubmed: 23382677
Ophthalmic Res. 1994;26(5):310-23
pubmed: 7533278
J Neurol Sci. 1995 Dec;134 Suppl:33-44
pubmed: 8847543
Cell Mol Life Sci. 2014 May;71(9):1607-22
pubmed: 24218010
J Magn Reson Imaging. 2016 Aug;44(2):426-32
pubmed: 26800367
Glia. 2009 Apr 1;57(5):467-78
pubmed: 18837051
Neurobiol Dis. 2015 Sep;81:66-75
pubmed: 25771171
J Neuroimmunol. 2017 Mar 15;304:86-92
pubmed: 27743612
J Neurosci Methods. 2016 Jan 15;257:55-63
pubmed: 26365332
Cell Mol Biol (Noisy-le-grand). 2000 Jun;46(4):865-9
pubmed: 10875447
Clin Exp Pharmacol Physiol. 2017 Mar;44(3):327-334
pubmed: 28004401
Biometals. 2016 Aug;29(4):573-91
pubmed: 27457588
Acta Neuropathol. 2017 Jan;133(1):25-42
pubmed: 27796537
J Neuroimmunol. 1988 Jan;17(2):127-35
pubmed: 2447124
PLoS One. 2015 Jul 17;10(7):e0128386
pubmed: 26186349
Mult Scler. 2015 Nov;21(13):1693-704
pubmed: 25662351
Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):E4922-30
pubmed: 24282296
Biomolecules. 2015 May 11;5(2):808-47
pubmed: 25970586
Oxid Med Cell Longev. 2015;2015:725370
pubmed: 26106458
J Neuropathol Exp Neurol. 2009 Apr;68(4):341-55
pubmed: 19337065
Dan Med Bull. 2002 Nov;49(4):279-301
pubmed: 12553165
Cell Death Differ. 2016 Mar;23(3):369-79
pubmed: 26794443
Mol Neurobiol. 2016 Dec;53(10):7237-7253
pubmed: 26687231
Ann Neurol. 2013 Dec;74(6):848-61
pubmed: 23868451
J Neuropathol Exp Neurol. 2014 Aug;73(8):780-8
pubmed: 25007244
Neuron. 2014 Sep 3;83(5):1098-116
pubmed: 25132469
Oxid Med Cell Longev. 2016;2016:1973834
pubmed: 27829982
J Vis Exp. 2016 Dec 6;(118):
pubmed: 28060281
Curr Neuropharmacol. 2018;16(10):1484-1498
pubmed: 29318974
Future Med Chem. 2010 Jan;2(1):51-64
pubmed: 20161623
J Neurosci. 2012 Apr 4;32(14):4841-7
pubmed: 22492039
J Exp Med. 1984 Nov 1;160(5):1532-43
pubmed: 6333485
J Magn Reson Imaging. 2012 Jul;36(1):73-83
pubmed: 22407571
Ann Neurol. 2013 Nov;74(5):669-78
pubmed: 23813441
J Exp Med. 2015 Apr 6;212(4):481-95
pubmed: 25779633
Science. 2004 Dec 17;306(5704):2090-3
pubmed: 15514116
N Engl J Med. 2018 Jan 11;378(2):169-180
pubmed: 29320652
J Neurochem. 2007 Dec;103(5):1730-40
pubmed: 17953660
J Clin Invest. 2009 May;119(5):1159-66
pubmed: 19352007
J Neuroimmunol. 1998 Apr 15;84(2):188-97
pubmed: 9628462
Glia. 1996 Jun;17(2):83-93
pubmed: 8776576
Inorg Chem. 2013 Nov 4;52(21):12223-33
pubmed: 24102308
Biochim Biophys Acta. 2010 Aug;1800(8):783-92
pubmed: 20176086
Exp Neurol. 2009 Jul;218(1):64-74
pubmed: 19374902
Neurobiol Dis. 2015 Sep;81:93-107
pubmed: 25724358
Neurobiol Dis. 2015 Sep;81:108-18
pubmed: 25801802
Nature. 1984 Nov 8-14;312(5990):162-3
pubmed: 6095085
Proc Natl Acad Sci U S A. 2018 Oct 30;115(44):11292-11297
pubmed: 30322946
Cell. 2014 Jul 17;158(2):383-396
pubmed: 25018103
AJNR Am J Neuroradiol. 2016 Jul;37(7):1223-30
pubmed: 27012298
Brain. 2011 Dec;134(Pt 12):3602-15
pubmed: 22171355
J Neuropathol Exp Neurol. 2017 Jun 1;76(6):467-478
pubmed: 28505283
Neurosci Lett. 2011 Aug 1;500(1):36-40
pubmed: 21683124
Annu Rev Nutr. 2010 Aug 21;30:105-22
pubmed: 20420524
Biofactors. 2010 Mar-Apr;36(2):98-102
pubmed: 20336710
J Neuroimmune Pharmacol. 2010 Jun;5(2):220-30
pubmed: 19826959