Oligodendroglia metabolically support axons and contribute to neurodegeneration.

Détails

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Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_1604C69BA0EC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Oligodendroglia metabolically support axons and contribute to neurodegeneration.
Périodique
Nature
Auteur(s)
Lee Y., Morrison B.M., Li Y., Lengacher S., Farah M.H., Hoffman P.N., Liu Y., Tsingalia A., Jin L., Zhang P.W., Pellerin L., Magistretti P.J., Rothstein J.D.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Statut éditorial
Publié
Date de publication
07/2012
Peer-reviewed
Oui
Volume
487
Numéro
7408
Pages
443-448
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Résumé
Oligodendroglia support axon survival and function through mechanisms independent of myelination, and their dysfunction leads to axon degeneration in several diseases. The cause of this degeneration has not been determined, but lack of energy metabolites such as glucose or lactate has been proposed. Lactate is transported exclusively by monocarboxylate transporters, and changes to these transporters alter lactate production and use. Here we show that the most abundant lactate transporter in the central nervous system, monocarboxylate transporter 1 (MCT1, also known as SLC16A1), is highly enriched within oligodendroglia and that disruption of this transporter produces axon damage and neuron loss in animal and cell culture models. In addition, this same transporter is reduced in patients with, and in mouse models of, amyotrophic lateral sclerosis, suggesting a role for oligodendroglial MCT1 in pathogenesis. The role of oligodendroglia in axon function and neuron survival has been elusive; this study defines a new fundamental mechanism by which oligodendroglia support neurons and axons.
Mots-clé
Amyotrophic Lateral Sclerosis/genetics, Amyotrophic Lateral Sclerosis/metabolism, Animals, Axons/metabolism, Axons/pathology, Cell Line, Cell Survival, Disease Models, Animal, Down-Regulation, Heterozygote, Humans, Lactic Acid/metabolism, Mice, Mice, Transgenic, Monocarboxylic Acid Transporters/deficiency, Monocarboxylic Acid Transporters/genetics, Motor Neurons/metabolism, Motor Neurons/pathology, Myelin Sheath/metabolism, Nerve Degeneration/metabolism, Oligodendroglia/metabolism, Protein Transport, RNA, Small Interfering, Superoxide Dismutase/genetics, Superoxide Dismutase/metabolism, Symporters/deficiency, Symporters/genetics
Pubmed
Web of science
Création de la notice
28/08/2012 11:08
Dernière modification de la notice
20/08/2019 13:45
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