Distribution of monocarboxylate transporters in the peripheral nervous system suggests putative roles in lactate shuttling and myelination

• Published in: The Journal of neuroscience Vol. 35; no. 10; pp. 4151 - 4156
• Main Authors: Domènech-Estévez, Enric, Baloui, Hasna, Repond, Cendrine, Rosafio, Katia, Médard, Jean-Jacques, Tricaud, Nicolas, Pellerin, Luc, Chrast, Roman
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 11.03.2015
• Subjects: Actins - metabolism; Age Factors; Animals; Animals, Newborn; Brief Communications; Cell Adhesion Molecules, Neuronal - metabolism; Cells, Cultured; Coculture Techniques; Early Growth Response Protein 2 - genetics; Embryo, Mammalian; Ganglia, Spinal - cytology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Humans; In Vitro Techniques; Lactic Acid - metabolism; Lactic Acid - pharmacology; Male; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Monocarboxylic Acid Transporters - classification; Monocarboxylic Acid Transporters - genetics; Monocarboxylic Acid Transporters - metabolism; Myelin Basic Protein - metabolism; Myelin P0 Protein - genetics; Myelin Sheath - metabolism; Neurofilament Proteins - metabolism; Peripheral Nerves - cytology; Peripheral Nerves - metabolism; Rats; Rats, Sprague-Dawley; Schwann Cells - drug effects; Schwann Cells - metabolism; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - metabolism; peripheral nervous system; lactate; monocarboxylate transporters; Schwann cells
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/jneurosci.3534-14.2015

Lactate, a product of glycolysis, has been shown to play a key role in the metabolic support of neurons/axons in the CNS by both astrocytes and oligodendrocytes through monocarboxylate transporters (MCTs). Despite such importance in the CNS, little is known about MCT expression and lactate function in the PNS. Here we show that mouse MCT1, MCT2, and MCT4 are expressed in the PNS. While DRG neurons express MCT1, myelinating Schwann cells (SCs) coexpress MCT1 and MCT4 in a domain-specific fashion, mainly in regions of noncompact myelin. Interestingly, SC-specific downregulation of MCT1 expression in rat neuron/SC cocultures led to increased myelination, while its downregulation in neurons resulted in a decreased amount of neurofilament. Finally, pure rat SCs grown in the presence of lactate exhibited an increase in the level of expression of the main myelin regulator gene Krox20/Egr2 and the myelin gene P0. These data indicate that lactate homeostasis participates in the regulation of the SC myelination program and reveal that similar to CNS, PNS axon-glial metabolic interactions are most likely mediated by MCTs.