Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity

By U. Fünfschilling, Lotti M Supplie, D. Mahad, S. Boretius, Aiman S. Saab, J. Edgar, Bastian G Brinkmann, C. Kassmann, Iva D. Tzvetanova, W. Möbius and 9 more. Nature, 2012

1,419 citations recorded by the source corpus.

Oligodendrocytes, the myelin-forming glial cells of the central nervous system, maintain long-term axonal integrity. However, the underlying support mechanisms are not understood. Here we identify a metabolic component of axon–glia interactions by generating conditional Cox10 (protoheme IX farnesyltransferase) mutant mice, in which oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX, also known as mitochondrial complex IV). In the peripheral nervous system, Cox10 conditional mutants exhibit severe neuropathy with dysmyelination, abnormal Remak bundles, muscle atrophy and paralysis. Notably, perturbing mitochondrial respiration did not cause glial cell death. In the adult central nervous system, we found no signs of demyelination, axonal degeneration or secondary inflammation. Unlike cultured oligodendrocytes, which are sensitive to COX inhibitors, post-myelination oligodendrocytes survive well in the absence of COX activity. More importantly, by in vivo magnetic resonance spectroscopy, brain lactate concentrations in mutants were increased compared with controls, but were detectable only in mice exposed to volatile anaesthetics. This indicates that aerobic glycolysis products derived from oligodendrocytes are rapidly metabolized within white matter tracts. Because myelinated axons can use lactate when energy-deprived, our findings suggest a model in which axon–glia metabolic coupling serves a physiological function.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/09334fac2e46fe45d0538444ebee729107767091

How researchers see this paper

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

In Cellular and Molecular Neuroscience

1. G. Dienel
2. Igor Allaman
3. M. Simons
4. A. Tran
5. P. Warren
6. Pierre J. Magistretti
7. F. Kirchhoff
8. J. Silver

In Developmental Neuroscience

1. M. Simons
2. F. Kirchhoff
3. J. Silver
4. Igor Allaman
5. A. Tran
6. K. Nave
7. Pierre J. Magistretti

In Neurology

1. M. Simons
2. Igor Allaman
3. G. Dienel
4. F. Kirchhoff
5. K. Nave
6. Pierre J. Magistretti
7. R. Ransohoff

Citations in the corpus

• 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].”
• The Biology of Regeneration Failure and Success After Spinal Cord Injury. (2018, background): “Following SCI, the abundance of NG2 OPCs in the lesion penumbra may be providing a safe haven in the midst of fulminant inflammation that serves to stabilize the severed axonal ending through this unusual glia/neuron bond and, unfortunately, helping to prevent them from regenerating further (48, 112”
• 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].”
• A cellular perspective on brain energy metabolism and functional imaging. (2015, background): “…gap junctions), resulting in an impairment in the delivery of lactate, produces axonal damage and neuronal loss in animal and cell-culture models (Fünfschilling et al., 2012; Lee et al., 2012), an observation that may be relevant to the pathophysiology of amyotrophic lateral sclerosis (Lee et…”