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Pyruvate and lactate can shuttle between glial cells and axons via monocarboxylate transporters. However, lactate can only be synthesized or used in metabolic reactions with the help of lactate dehydrogenase (LDH), a tetramer of LDHA and LDHB subunits in varying compositions. Here we show that mice with a cell type\u2010specific disruption of both <jats:italic>Ldha<\/jats:italic> and <jats:italic>Ldhb<\/jats:italic> genes in oligodendrocytes lack a pathological phenotype that would be indicative of oligodendroglial dysfunctions or lack of axonal metabolic support. Indeed, when combining immunohistochemical, electron microscopical, and in situ hybridization analyses in adult mice, we found that the vast majority of mature oligodendrocytes lack detectable expression of LDH. Even in neurodegenerative disease models and in mice under metabolic stress LDH was not increased. In contrast, at early development and in the remyelinating brain, LDHA was readily detectable in immature oligodendrocytes. Interestingly, by immunoelectron microscopy LDHA was particularly enriched at gap junctions formed between adjacent astrocytes and at junctions between astrocytes and oligodendrocytes. Our data suggest that oligodendrocytes metabolize lactate during development and remyelination. In contrast, for metabolic support of axons mature oligodendrocytes may export their own glycolysis products as pyruvate rather than lactate. Lacking LDH, these oligodendrocytes can also \u201cfunnel\u201d lactate through their \u201cmyelinic\u201d channels between gap junction\u2010coupled astrocytes and axons without metabolizing it. We suggest a working model, in which the unequal cellular distribution of LDH in white matter tracts facilitates a rapid and efficient transport of glycolysis products among glial and axonal compartments.<\/jats:p>","DOI":"10.1002\/glia.24533","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T10:30:21Z","timestamp":1712572221000},"page":"1374-1391","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons"],"prefix":"10.1002","volume":"72","author":[{"given":"Erik","family":"Sp\u00e4te","sequence":"first","affiliation":[{"name":"Department of Neurogenetics Max Planck Institute for Multidisciplinary Sciences  G\u00f6ttingen 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