Mature oligodendrocytes bordering lesions limit demyelination and favor myelin repair via heparan sulfate production.
Animals
Corpus Callosum
/ metabolism
Demyelinating Diseases
/ chemically induced
Disease Models, Animal
Gene Deletion
HEK293 Cells
Hedgehog Proteins
/ metabolism
Heparitin Sulfate
/ metabolism
Humans
Lysophosphatidylcholines
Macrophage Activation
Mice, Transgenic
Microglia
/ metabolism
Multiple Sclerosis
/ metabolism
Oligodendroglia
/ metabolism
Remyelination
Sulfotransferases
/ genetics
Up-Regulation
Human
Ndst1
heparan sulfate
microglia
mouse
multiple sclerosis
myelin
neuroscience
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
09 06 2020
09 06 2020
Historique:
received:
17
09
2019
accepted:
09
06
2020
pubmed:
10
6
2020
medline:
4
3
2021
entrez:
10
6
2020
Statut:
epublish
Résumé
Myelin destruction is followed by resident glia activation and mobilization of endogenous progenitors (OPC) which participate in myelin repair. Here we show that in response to demyelination, mature oligodendrocytes (OLG) bordering the lesion express Ndst1, a key enzyme for heparan sulfates (HS) synthesis. Ndst1+ OLG form a belt that demarcates lesioned from intact white matter. Mice with selective inactivation of Ndst1 in the OLG lineage display increased lesion size, sustained microglia and OPC reactivity. HS production around the lesion allows Sonic hedgehog (Shh) binding and favors the local enrichment of this morphogen involved in myelin regeneration. In MS patients, Ndst1 is also found overexpressed in oligodendroglia and the number of Ndst1-expressing oligodendroglia is inversely correlated with lesion size and positively correlated with remyelination potential. Our study suggests that mature OLG surrounding demyelinated lesions are not passive witnesses but contribute to protection and regeneration by producing HS.
Identifiants
pubmed: 32515730
doi: 10.7554/eLife.51735
pii: 51735
pmc: PMC7308090
doi:
pii:
Substances chimiques
Hedgehog Proteins
0
Lysophosphatidylcholines
0
Shh protein, mouse
0
Heparitin Sulfate
9050-30-0
Sulfotransferases
EC 2.8.2.-
heparitin sulfotransferase
EC 2.8.2.8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MR/K017047/1
Pays : United Kingdom
Organisme : Agence Nationale de la Recherche
ID : ANR-15-CE16-0014-01
Pays : International
Organisme : AM*DEX NeuroMarseille Institute
ID : AMX-19-IET-004
Pays : International
Organisme : Fondation pour la Recherche Médicale
ID : DEQ20140329501
Pays : International
Informations de copyright
© 2020, Macchi et al.
Déclaration de conflit d'intérêts
MM, KM, CZ, EP, BE, BB, SJ, KG, FK, AW, MC, PD No competing interests declared
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