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  Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity.

Fünfschilling, U., Supplie, L. M., Mahad, D., Boretius, S., Saab, A., Edgar, J., et al. (2012). Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature, 485(7399), 517-521. doi:10.1038/nature11007.

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Fünfschilling, U., Autor
Supplie, L. M., Autor
Mahad, D., Autor
Boretius, S.1, Autor           
Saab, A., Autor
Edgar, J., Autor
Brinkmann, B. G., Autor
Kassmann, C. M., Autor
Tzvetanova, I. D., Autor
Möbius, W., Autor
Diaz, F., Autor
Meijer, D., Autor
Suter, U., Autor
Hamprecht, B., Autor
Sereda, M. W., Autor
Moraes, C. T., Autor
Frahm, J.1, Autor           
Goebbels, S., Autor
Nave, K. A., Autor
Affiliations:
1Biomedical NMR Research GmbH, MPI for biophysical chemistry, Max Planck Society, ou_578634              

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 Zusammenfassung: Oligodendrocytes, the myelin-forming glial cells of the central nervous system, maintain long-term axonal integrity1, 2, 3. However, the underlying support mechanisms are not understood4. 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 inhibitors5, 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-deprived6, our findings suggest a model in which axon–glia metabolic coupling serves a physiological function.

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Sprache(n): eng - English
 Datum: 2012-04-292012-05-24
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1038/nature11007
 Art des Abschluß: -

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Titel: Nature
Genre der Quelle: Zeitschrift
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Seiten: - Band / Heft: 485 (7399) Artikelnummer: - Start- / Endseite: 517 - 521 Identifikator: -