Oligodendroglia metabolically support axons and contribute to neurodegeneration.
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.
Department of Neurology, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
Youngjin
Y
Lee
Brett M
BM
Morrison
Yun
Y
Li
Sylvain
S
Lengacher
Mohamed H
MH
Farah
Paul N
PN
Hoffman
Yiting
Y
Liu
Akivaga
A
Tsingalia
Lin
L
Jin
Ping-Wu
PW
Zhang
Luc
L
Pellerin
Pierre J
PJ
Magistretti
Jeffrey D
JD
Rothstein
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival; D004195:Disease Models, Animal; D015536:Down-Regulation; D006579:Heterozygote; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D027501:Monocarboxylic Acid Transporters / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D009186:Myelin Sheath / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D021381:Protein Transport; D034741:RNA, Small Interfering; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D027981:Symporters / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000099233:Monocarboxylate Transport Protein 1
D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D034741:RNA, Small Interfering; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse