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Monocarboxylate transporter 2 regulates maintenance of myelin and axonal integrity by oligodendrocytes | Nature Communications
Myelin alterations, tightly linked to axonal degeneration, are common in neurodegenerative diseases, including multiple sclerosis (MS). However, the metabolic mechanisms that sustain white matter integrity remain elusive. Monocarboxylates are important energy fuels, but their role in myelinating oligodendrocyte function remains unclear. Here, we show that myelinating oligodendrocytes express high affinity monocarboxylate transporter 2 (MCT2), which is downregulated in progressive MS. While deletion of MCT2 in the mouse spinal white matter using oligodendrotropic AAV injection does not affect oligodendrocyte survival, it downregulates lipid synthesis-associated enzymes and increases inflammation, leading to a failure of myelin maintenance. These changes, not evidenced in AAV-control mice that only show mild inflammation, are accompanied by axonal upregulation of lactate dehydrogenase A and injury, effects alleviated by ketogenic diet. Therefore, our findings show that oligodendroglial M
