Oligodendroglia metabolically support axons and contribute to neurodegeneration

Youngjin Lee, Brett M. Morrison, Yun Li, Sylvain Lengacher, Mohamed H. Farah, Paul N. Hoffman, Yiting Liu, Akivaga Tsingalia, Lin Jin, Ping Wu Zhang, Luc Pellerin, Pierre J. Magistretti, Jeffrey D. Rothstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1183 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)443-448
Number of pages6
Issue number7408
StatePublished - Jul 26 2012

Bibliographical note

Funding Information:
Acknowledgements We thank C. Coccia, S. Vidensky, I. Shats, L. Chakravarti, Y. Ayukawa and L. Mamedova for technical support, E. Potter for oligodendrocyte cultures, C. Cooke for electron microscopy, and S. Kang and D. Bergles for providing MOBP–eGFP BAC and CNP BacTrap mice, CASPR and Nav1.6 antibodies. Autopsy specimens were provided by the Johns Hopkins ALS Tissue Bank and the Johns Hopkins University Brain Resource Center supported by National Institutes of Health grants P50AG05146 and PO1NS16375. Support was provided by the Muscular Dystrophy Association (B.M.M. and Yo.L.), NIH-NS33958 (J.D.R.), P2ALS (J.D.R.), Packard Center for ALS (J.D.R.), Human Frontier Science Program-RG118/1998-B (L.P.), Swiss Fonds National de Recherche Scientifique-31003A-125063 (L.P.), Swiss National Science Foundation (FNRS)-3100AO-108336/1 (P.J.M.), Biaggi and Puccini Foundations (P.J.M). We dedicate this manuscript to J. W. Griffin, who passed away while this manuscript was under revision, and are grateful for his contributions to this manuscript and mentorship to many of the authors on this paper.

ASJC Scopus subject areas

  • General


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