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Physiology of PNS axons relies on glycolytic metabolism in myelinating Schwann cells

While lactate shuttle theory states that glial cells metabolize glucose into lactate to shuttle it to neurons, how glial cells support axonal metabolism and function remains unclear. Lactate production is a common occurrence following anaerobic glycolysis in muscles. However, several other cell type...

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Autores principales: Deck, Marie, Van Hameren, Gerben, Campbell, Graham, Bernard-Marissal, Nathalie, Devaux, Jérôme, Berthelot, Jade, Lattard, Alise, Médard, Jean-Jacques, Gautier, Benoît, Guelfi, Sophie, Abbou, Scarlette, Quintana, Patrice, Chao de la Barca, Juan Manuel, Reynier, Pascal, Lenaers, Guy, Chrast, Roman, Tricaud, Nicolas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531822/
https://www.ncbi.nlm.nih.gov/pubmed/36194565
http://dx.doi.org/10.1371/journal.pone.0272097
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author Deck, Marie
Van Hameren, Gerben
Campbell, Graham
Bernard-Marissal, Nathalie
Devaux, Jérôme
Berthelot, Jade
Lattard, Alise
Médard, Jean-Jacques
Gautier, Benoît
Guelfi, Sophie
Abbou, Scarlette
Quintana, Patrice
Chao de la Barca, Juan Manuel
Reynier, Pascal
Lenaers, Guy
Chrast, Roman
Tricaud, Nicolas
author_facet Deck, Marie
Van Hameren, Gerben
Campbell, Graham
Bernard-Marissal, Nathalie
Devaux, Jérôme
Berthelot, Jade
Lattard, Alise
Médard, Jean-Jacques
Gautier, Benoît
Guelfi, Sophie
Abbou, Scarlette
Quintana, Patrice
Chao de la Barca, Juan Manuel
Reynier, Pascal
Lenaers, Guy
Chrast, Roman
Tricaud, Nicolas
author_sort Deck, Marie
collection PubMed
description While lactate shuttle theory states that glial cells metabolize glucose into lactate to shuttle it to neurons, how glial cells support axonal metabolism and function remains unclear. Lactate production is a common occurrence following anaerobic glycolysis in muscles. However, several other cell types, including some stem cells, activated macrophages and tumor cells, can produce lactate in presence of oxygen and cellular respiration, using Pyruvate Kinase 2 (PKM2) to divert pyruvate to lactate dehydrogenase. We show here that PKM2 is also upregulated in myelinating Schwann cells (mSC) of mature mouse sciatic nerve versus postnatal immature nerve. Deletion of this isoform in PLP-expressing cells in mice leads to a deficit of lactate in mSC and in peripheral nerves. While the structure of myelin sheath was preserved, mutant mice developed a peripheral neuropathy. Peripheral nerve axons of mutant mice failed to maintain lactate homeostasis upon activity, resulting in an impaired production of mitochondrial ATP. Action potential propagation was not altered but axonal mitochondria transport was slowed down, muscle axon terminals retracted and motor neurons displayed cellular stress. Additional reduction of lactate availability through dichloroacetate treatment, which diverts pyruvate to mitochondrial oxidative phosphorylation, further aggravated motor dysfunction in mutant mice. Thus, lactate production through PKM2 enzyme and aerobic glycolysis is essential in mSC for the long-term maintenance of peripheral nerve axon physiology and function.
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spelling pubmed-95318222022-10-05 Physiology of PNS axons relies on glycolytic metabolism in myelinating Schwann cells Deck, Marie Van Hameren, Gerben Campbell, Graham Bernard-Marissal, Nathalie Devaux, Jérôme Berthelot, Jade Lattard, Alise Médard, Jean-Jacques Gautier, Benoît Guelfi, Sophie Abbou, Scarlette Quintana, Patrice Chao de la Barca, Juan Manuel Reynier, Pascal Lenaers, Guy Chrast, Roman Tricaud, Nicolas PLoS One Research Article While lactate shuttle theory states that glial cells metabolize glucose into lactate to shuttle it to neurons, how glial cells support axonal metabolism and function remains unclear. Lactate production is a common occurrence following anaerobic glycolysis in muscles. However, several other cell types, including some stem cells, activated macrophages and tumor cells, can produce lactate in presence of oxygen and cellular respiration, using Pyruvate Kinase 2 (PKM2) to divert pyruvate to lactate dehydrogenase. We show here that PKM2 is also upregulated in myelinating Schwann cells (mSC) of mature mouse sciatic nerve versus postnatal immature nerve. Deletion of this isoform in PLP-expressing cells in mice leads to a deficit of lactate in mSC and in peripheral nerves. While the structure of myelin sheath was preserved, mutant mice developed a peripheral neuropathy. Peripheral nerve axons of mutant mice failed to maintain lactate homeostasis upon activity, resulting in an impaired production of mitochondrial ATP. Action potential propagation was not altered but axonal mitochondria transport was slowed down, muscle axon terminals retracted and motor neurons displayed cellular stress. Additional reduction of lactate availability through dichloroacetate treatment, which diverts pyruvate to mitochondrial oxidative phosphorylation, further aggravated motor dysfunction in mutant mice. Thus, lactate production through PKM2 enzyme and aerobic glycolysis is essential in mSC for the long-term maintenance of peripheral nerve axon physiology and function. Public Library of Science 2022-10-04 /pmc/articles/PMC9531822/ /pubmed/36194565 http://dx.doi.org/10.1371/journal.pone.0272097 Text en © 2022 Deck et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Deck, Marie
Van Hameren, Gerben
Campbell, Graham
Bernard-Marissal, Nathalie
Devaux, Jérôme
Berthelot, Jade
Lattard, Alise
Médard, Jean-Jacques
Gautier, Benoît
Guelfi, Sophie
Abbou, Scarlette
Quintana, Patrice
Chao de la Barca, Juan Manuel
Reynier, Pascal
Lenaers, Guy
Chrast, Roman
Tricaud, Nicolas
Physiology of PNS axons relies on glycolytic metabolism in myelinating Schwann cells
title Physiology of PNS axons relies on glycolytic metabolism in myelinating Schwann cells
title_full Physiology of PNS axons relies on glycolytic metabolism in myelinating Schwann cells
title_fullStr Physiology of PNS axons relies on glycolytic metabolism in myelinating Schwann cells
title_full_unstemmed Physiology of PNS axons relies on glycolytic metabolism in myelinating Schwann cells
title_short Physiology of PNS axons relies on glycolytic metabolism in myelinating Schwann cells
title_sort physiology of pns axons relies on glycolytic metabolism in myelinating schwann cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531822/
https://www.ncbi.nlm.nih.gov/pubmed/36194565
http://dx.doi.org/10.1371/journal.pone.0272097
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