The study investigates the role of glycolytic oligodendrocytes in maintaining myelin and long-term axonal integrity. By generating conditional Cox10 mutant mice, the researchers found that oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX), leading to severe neuropathy in the peripheral nervous system with dysmyelination, abnormal Remak bundles, muscle atrophy, and paralysis. However, in the adult central nervous system, no signs of demyelination, axonal degeneration, or secondary inflammation were observed. The absence of COX activity did not cause glial cell death, and mature oligodendrocytes survived well in the absence of COX activity. In vivo magnetic resonance spectroscopy revealed increased brain lactate concentrations in uninfected mice, which were detectable only under isoflurane anesthesia. This indicates that aerobic glycolysis products from oligodendrocytes are rapidly metabolized within white matter tracts. The findings suggest that axon-glial metabolic coupling serves a physiological function, where myelinated axons can use lactate as an energy source when energy-deprived. The study also highlights the mild post-myelination CNS phenotype of adult Cox10 mutant mice, where oligodendrocytes maintain myelin and their ensheathed axons, likely through enhanced glycolysis.The study investigates the role of glycolytic oligodendrocytes in maintaining myelin and long-term axonal integrity. By generating conditional Cox10 mutant mice, the researchers found that oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX), leading to severe neuropathy in the peripheral nervous system with dysmyelination, abnormal Remak bundles, muscle atrophy, and paralysis. However, in the adult central nervous system, no signs of demyelination, axonal degeneration, or secondary inflammation were observed. The absence of COX activity did not cause glial cell death, and mature oligodendrocytes survived well in the absence of COX activity. In vivo magnetic resonance spectroscopy revealed increased brain lactate concentrations in uninfected mice, which were detectable only under isoflurane anesthesia. This indicates that aerobic glycolysis products from oligodendrocytes are rapidly metabolized within white matter tracts. The findings suggest that axon-glial metabolic coupling serves a physiological function, where myelinated axons can use lactate as an energy source when energy-deprived. The study also highlights the mild post-myelination CNS phenotype of adult Cox10 mutant mice, where oligodendrocytes maintain myelin and their ensheathed axons, likely through enhanced glycolysis.