Oligodendroglia metabolically support axons and contribute to neurodegeneration

By Youngjin Lee, B. Morrison, Yun Li, S. Lengacher, Mohamed H. Farah, P. Hoffman, Yiting Liu, Akivaga Tsingalia, Lin Jin, Ping-Wu Zhang and 3 more. Nature, 2012

1,583 citations recorded by the source corpus.

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.

Subfields: Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/631581d8237136ceadac007ed9c4a57cb1f9fb35

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Neurology

1. V. Lee
2. John Q. Trojanowski
3. K. Del Tredici
4. H. Braak
5. M. Simons
6. F. Kirchhoff
7. G. Dienel
8. K. Nave

In Physiology

1. John Q. Trojanowski
2. K. Del Tredici
3. V. Lee
4. H. Braak
5. G. Dienel
6. Dennis W. Dickson
7. D. Holtzman
8. M. Goedert

Citations in the corpus

• Brain metabolism in health, aging, and neurodegeneration (2017, neutral): “Nature 487: 443 – 448 Leonardi A, Abbruzzese G, Arata L, Cocito L, Vische M (1984) Cerebrospinal fluid (CSF) findings in amyotrophic lateral sclerosis.”
• Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte–Neuron Communication (2013, background): “such as lactate and furthermore, interference with oligodendroglial lactate export results in axonal degeneration [8,9].”
• An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases (2019, background): “Oligodendrocytes are myelin-producing cells that provide metabolic support for neurons and prevent neurodegeneration [78].”
• Oligodendrocytes: Myelination and Axonal Support. (2015, background): “Interestingly, even 50% reduced expression of MCT1 (in heterozygous mouse mutants) interferes with long-term maintenance of myelinated axons (Lee et al. 2012), similar in phenotype to axonal degeneration caused by oligodendrocyte-specific defects (Griffiths et al.”
• Sugar for the brain: the role of glucose in physiological and pathological brain function (2013, background): “In the brain, defective lactate transporter levels in oligodendrocytes are linked to axonopathy [34] (Figure 1c), and in the peripheral nervous system disrupted oxidative phosphorylation in Schwann cells is related to severe neuropathy [33].”
• Stages of pTDP‐43 pathology in amyotrophic lateral sclerosis (2013, background): “Different ALS syndromes were defined according to clinical onset of disease: cervical lower motor neuron ALS, lumbar lower motor neuron ALS, lumbar upper motor neuron ALS, bulbar lower motor neuron (BLMN) ALS, and bulbar upper motor neuron (BUMN) ALS.19 None of the cases in the cohort had cervical u”